Objective: This study was to investigate the role of hsa-miR-155-3p and hsa-miR-155-5p as biomarkers and regulators of biological behavior in Systemic Sclerosis. Methods: A total of 10 SSc patients and 10 healthy cont...Objective: This study was to investigate the role of hsa-miR-155-3p and hsa-miR-155-5p as biomarkers and regulators of biological behavior in Systemic Sclerosis. Methods: A total of 10 SSc patients and 10 healthy controls were selected for the study. The expression levels of hsa-miR-155-3p and hsa-miR-155-5p in peripheral blood mononuclear cells of SSc patients and healthy controls were measured using RT-qPCR. The diagnostic value of these miRNAs was explored using Receiver Operating Characteristic curve analysis. Pearson or Spearman correlation analysis was performed to assess the correlation between miRNAs and clinical indicators in SSc patients. Potential target genes of hsa-miR-155-3p and hsa-miR-155-5p were predicted using miRDB, Targetscan, and miRDIP databases. GO functional annotation, KEGG pathway enrichment analysis, protein-protein interaction network construction, and selection of central genes were conducted. Results: The expression levels of hsa-miR-155-3p and hsa- miR-155-5p were significantly higher in PBMCs of SSc patients compared to healthy controls (P<0.001). The ROC curve analysis showed that hsa-miR-155-3p and hsa-miR-155-5p had a high diagnostic value for SSc (AUC=1, P<0.001). Correlation analysis revealed that hsa- miR-155-3p, hsa-miR-155-5p, and clinical indicators such as high-resolution CT, neutrophil percentage, lymphocyte percentage, and albumin to globulin ratio were correlated (P<0.05). The signaling pathways enriched with target genes of hsa-miR-155-3p and hsa-miR-155- 5p were closely associated with the occurrence and development of SSc fibrosis, immunity, and inflammation. Conclusions: hsa-miR-155-3p and hsa-miR-155-5p may be involved in regulating the occurrence and development of SSc fibrosis, immunity, and inflammation. They have the potential to serve as biomarkers for clinical diagnosis and treatment of SSc.展开更多
Scleroderma is a rare disease with two primary forms: localized scleroderma (LS) and systemic sclerosis (SSc). Both are chronic conditions that can manifest in various patterns (subtypes) and are linked to extracutane...Scleroderma is a rare disease with two primary forms: localized scleroderma (LS) and systemic sclerosis (SSc). Both are chronic conditions that can manifest in various patterns (subtypes) and are linked to extracutaneous involvement in pediatric patients. Juvenile SSc poses a higher risk of morbidity and mortality, with patients facing life-threatening complications such as lung, heart, and visceral organ fibrosis, and vasculopathy. In contrast, mortality is extremely rare in juvenile LS, but patients are susceptible to significant morbidity, leading to severe disfigurement and functional impairment. Treatment for scleroderma aims to control inflammation and address specific issues. An early diagnosis significantly enhances the overall outcome. This study conducts a retrospective descriptive analysis aiming to document the clinical manifestations, management approaches, and outcomes of systemic sclerosis in a cohort of nine children receiving treatment for juvenile systemic sclerosis at Pediatric B department of Mohammed VI University, Hospital Center in Marrakech, Morocco.展开更多
Adipose-derived stem cells(ADSCs)residing in the stromal vascular fraction(SVF)of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis(SSc),a complex conn...Adipose-derived stem cells(ADSCs)residing in the stromal vascular fraction(SVF)of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis(SSc),a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular lesions.Several preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous manifestations of SSc patients.However,currently available data indicate that ADSCs may represent a double-edged sword in SSc,as they may exhibit a pro-fibrotic and anti-adipogenic phenotype,possibly behaving as an additional pathogenic source of pro-fibrotic myofibroblasts through the adipocyte-to-myofibroblast transition process.Thus,in the perspective of a larger employ of SSc-ADSCs for further therapeutic applications,it is important to definitely unravel whether these cells present a comparable phenotype and similar immunosuppressive,anti-inflammatory,anti-fibrotic and pro-angiogenic properties in respect to healthy ADSCs.In light of the dual role that ADSCs seem to play in SSc,this review will provide a summary of the most recent insights into the preclinical and clinical studies employing SVF and ADSCs for the treatment of the disease and,at the same time,will focus on the main findings highlighting the possible involvement of these stem cells in SSc-related fibrosis pathogenesis.展开更多
Systemic sclerosis is an autoimmune disease characterized by vascular disease,fibrosis of the skin,and internal organ dysfunction.Gastrointestinal involvement is the most frequent complication of internal organs,impac...Systemic sclerosis is an autoimmune disease characterized by vascular disease,fibrosis of the skin,and internal organ dysfunction.Gastrointestinal involvement is the most frequent complication of internal organs,impacting up to 90%of patients.Gastrointestinal involvement can affect any region of the gastrointestinal tract from the mouth to the anus,with a predominance of disorders being observed at the level of the upper digestive tract.The gastrointestinal involvement primarily involves the esophagus,small bowel,and rectum.The severity of gastrointestinal involvement affects quality of life and is a marker of worse prognosis and mortality in these patients.In this review,we describe the current findings regarding gastrointestinal involvement by this entity.展开更多
Background:To explore the relevant targets of the Chinese herbal medicine compound Danggui-Sini Decoction(DGSND)for the treatment of systemic sclerosis(SSc).Method:We used TCMSP to enlist ingredients and Swiss Target ...Background:To explore the relevant targets of the Chinese herbal medicine compound Danggui-Sini Decoction(DGSND)for the treatment of systemic sclerosis(SSc).Method:We used TCMSP to enlist ingredients and Swiss Target Prediction for targets fishing,and the protein names by UniProt for organized as gene symbol.Strawberry Perl was used to integrate the active ingredients and the drugs action target of DGSND,with Cytoscape 3.9.0 software to construct"Active ingredient-Drug target"network.Then,GEO database,GeneCards database,TTDdatabase,DisGENent database and MalaCards database for SSc-related disease target prediction,and then analyzed the active drug targets of DGSND and SSc-related targets of Danggui-Sini Decoction treat SSc.Then,the above results we combined with STRING database to visualize the Protein-protein interaction(PPI)network for the core targets of SSc,and performed Gene ontology(GO)functional analysis and Kyoto Encyclopedia of Genomics(KEGG)signaling pathway enrichment analysis for SSc-related targets treated with DGSND Result:DGSND contains 223 active ingredients including Sitogluside,Benzoylpaeoniflorin,(-)-Asarinin Palbinone,Glycyro,4'DMEP etc.which acts on Signal transducer and activator of transcription 3(STAT3),Tumor Necrosis Factor(TNF),Vascular endothelial growth factor(VEGFA),Nuclear factor kappa-B(NFκB1),Interleukin(IL1β,IL17),Mitogen-activated protein kinase(MAPK)and Janus Kinase(JAK)and many other genes totaling 176,mainly involved in 4 more biological processes 3 molecular functions and 3 cellular components.Conclusion:DGSND is primarily used to treat SSc by regulating calcium homeostasis,inflammatory signaling pathways and neural cell repair and apoptosis-related pathways within the body.展开更多
Objective:To explore the molecular mechanism of Capparis spinosa in the treatment of systemic sclerosis((SSC))based on network pharmacology.Methods:GEO,Genecards,Pharmgkb,TTD and Drugbank databases were used to obtain...Objective:To explore the molecular mechanism of Capparis spinosa in the treatment of systemic sclerosis((SSC))based on network pharmacology.Methods:GEO,Genecards,Pharmgkb,TTD and Drugbank databases were used to obtain SSC targets,related literatures and Swisstargetprediction databases were used to obtain the main components of Citrus and their corresponding targets,and intersection was used to obtain prediction targets.Log in to the String database to analyze the protein interaction of the prediction target(PPI),further used Cytoscape to obtain the core gene by network topology analysis,and the core gene was docked with the main components of Capparis spinosa.The prediction targets were analyzed by gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis using R software.Results:A total of 15 active components and their targets were obtained,3171 SSC targets were obtained,and 66 predicted targets were obtained by intersection.Ten PPI core genes such as VEGFA,TNF,AKT1,PTGS2 and MMP9 were obtained by topological analysis.GO analysis involved many biological processes such as reactive oxygen species metabolic process、protein kinase B signaling、regulation of inflammatory response、phosphatidylinositol 3-kinase signaling and so on.KEGG pathway analysis showed PI3K-Akt signaling pathway,Proteoglycans in cancer,Focal adhesion,Rap1 signaling pathway and other signaling pathways.Conclusion:The molecular mechanism of Capparis spinosa in the treatment of SSC is predicted by the method of network pharmacology,which provides theoretical basis and data support for the basic research of Citrus officinalis in the treatment of SSC.展开更多
Introduction: Cutaneous manifestations of systemic sclerosis (SSc) include skin ulceration;4% - 12% of patients with SSc develop lower extremity ulcers of various etiologies. Limited data, significant morbidity, and s...Introduction: Cutaneous manifestations of systemic sclerosis (SSc) include skin ulceration;4% - 12% of patients with SSc develop lower extremity ulcers of various etiologies. Limited data, significant morbidity, and substantial cost of wound care led us to undertake this study to describe and identify risk factors. Methods: After Institutional Review Board approval, we identified 30 patients with SSc and lower extremity ulcers over a 10-year period at a single center with an SSc clinic, which were included in a descriptive analysis. Results: Median age of onset of lower extremity ulcers was 59.5 years (range 20 - 84). Ninety percent of patients were female, 60% were Caucasian, 63% had limited SSc, 13% diffuse SSc and 23% an overlap syndrome. Immunomodulators or steroids were prescribed in 53%;hypercoagulable state identified in 16%. Ulcers were attributed to venous stasis (27%), SSc (20%), trauma (20%), arterial disease (17%), and multifactorial/unknown (17%). In patients with ulcers attributed to SSc, age at onset was lower (45.5 vs 59.5 years). Biopsies generally did not contribute to management. Multidisciplinary treatment was routine;20% required amputation, 10% endovascular intervention, 20% frequent surgical debridement, 10% hyperbaric oxygen, 26% local treatment and antibiotics and 13% received immunosuppression for wound treatment. Conclusion: Lower extremity ulcers are a serious clinical problem in patients with SSc. The clinical exam, venous dopplers, ankle-brachial indices and assessment of vascular risk factors helped define causality. In younger patients, ulcers were more frequently attributed to SSc and these patients were more likely to be on immunosuppressants/DMARDS, possibly indicating severe phenotype of SSc.展开更多
Background:There is a dearth of mortality data on systemic sclerosis(SSc)in sub-Saharan Africa.We undertook a retrospective study of causes and predictors of death in low-income indigent South Africans with SSc.Method...Background:There is a dearth of mortality data on systemic sclerosis(SSc)in sub-Saharan Africa.We undertook a retrospective study of causes and predictors of death in low-income indigent South Africans with SSc.Methods:A retrospective records review of clinicodemographic,laboratory,and outcome data of SSc patients attending a state-funded tertiary Rheumatology service in South Africa.Results:Most of the 164 patients were Black(92.7%)and female(87.8%).The mean(SD)age at diagnosis and follow-up duration were 42.6(12.9)and 5.5(5.6)years,respectively.The majority(75.6%)had diffuse cutaneous SSc(dcSSc);and digital pits/ulcers,interstitial lung disease(ILD),and pulmonary hypertension(PH)were documented in 73.6%,55.0%,and 38.3%,respectively.There were 56 known deaths and an equal number of patients were lost to follow-up.Deaths resulted from ILD complicated by PH(42.9%),infections(8.9%),cardiac disease(7.1%),and malignancies(3.6%).Estimated 5-and 10-year survival rates for patients with known outcomes were 58%and 42%,respectively.Independent predictors of death were renal dysfunction and cor pulmonale.Conclusion:Most patients in this study of South Africans had dcSSc and poor outcomes.Known deaths resulted from cardiorespiratory complications of ILD complicated by PH.Cor pulmonale and renal dysfunction were independent predictors of death.展开更多
Objective:To examine the efficacy and safety of bathing therapy with Taohong Siwu Decoction(桃红四物汤,TSD) in the treatment of early-stage,mild-moderate diffuse cutaneous systemic sclerosis(dc SSc).Methods:This rando...Objective:To examine the efficacy and safety of bathing therapy with Taohong Siwu Decoction(桃红四物汤,TSD) in the treatment of early-stage,mild-moderate diffuse cutaneous systemic sclerosis(dc SSc).Methods:This randomized,placebo-controlled trial enrolled 148 men and women(18–60 years) with dc SSc(disease duration 12 months) and baseline modified Rodnan skin score(MRSS) 10.Patients were randomized into a TSD group(71 cases bathing with TSD plus oral prednisone) or control group(71 cases bathing with placebo plus oral prednisone).Bathing(40 ℃,30 min) of the upper and lower limbs was carried out once daily for 12 consecutive weeks.The primary outcome measure was MRSS;secondary outcomes were Raynaud's phenomenon(RP) score,quality of life(QOL),physician visual analogue scale(VAS),patient VAS,percent predicted diffusing capacity for carbon monoxide(DLCO),percent predicted forced vital capacity(FVC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP) level and overall treatment effect.Results:The final analysis included 135 patients(control group,68 cases;TSD group,67 cases).Primary and secondary outcome measures after 2 weeks of treatment showed no improvement(versus baseline) in both groups,with no differences between groups.At 12 weeks,QOL,physician VAS,patient VAS,ESR and CRP were improved in both groups,but MRSS and RP score were improved only in the TSD group(all P<0.05).MRSS,RP score,QOL,physician VAS,patient VAS,ESR and CRP differed significantly between groups(all P<0.05).Meanwhile,the overall treatment effect was significantly higher in the TSD group than in the control group(P<0.05).Adverse events in the two groups were similar(P>0.05).Conclusions:Bathing with TSD plus oral prednisone achieves better outcomes than oral prednisone alone in patients with dcS Sc and is not associated with serious adverse events.展开更多
Systemic sclerosis is a rare chronic autoimmune disease with extensive microvascular injury, damage of endothelialcells, activation of immune responses, and progression of tissue fibrosis in the skin and various inter...Systemic sclerosis is a rare chronic autoimmune disease with extensive microvascular injury, damage of endothelialcells, activation of immune responses, and progression of tissue fibrosis in the skin and various internal organs.According to epidemiological data, women’s populations are more susceptible to systemic sclerosis than men. Untilnow, various therapeutic options are employed to manage the symptoms of the disease. Since stem cell-basedtreatments have developed as a novel approach to rescue from several autoimmune diseases, it seems that stemcells, especially mesenchymal stem cells as a powerful regenerative tool can also be advantageous for systemicsclerosis treatment via their remarkable properties including immunomodulatory and anti-fibrotic effects.Accordingly, we discuss the contemporary status and future perspectives of mesenchymal stem cell transplantationfor systemic sclerosis.展开更多
As a novel cellular therapy, the anti-inflammatory and immunomodulatory virtues of mesenchymal stem cells (MSCs) make them promising candidates for systemic sclerosis (SSc) treatment. However, the clinical efficacy of...As a novel cellular therapy, the anti-inflammatory and immunomodulatory virtues of mesenchymal stem cells (MSCs) make them promising candidates for systemic sclerosis (SSc) treatment. However, the clinical efficacy of this stratagem is limited because of the short persistence time, poor survival, and engraftment of MSCs after injection in vivo. Herein, we develop a novel MSCs-laden injectable self-healing hydrogel for SSc treatment. The hydrogel is prepared using N, O-carboxymethyl chitosan (CS-CM) and 4-armed benzaldehyde-terminated poly-ethylene glycol (PEG-BA) as the main components, imparting with self-healing capacity via the reversible Schiff-base connection between the amino and benzaldehyde groups. We demonstrate that the hydrogel laden with MSCs not only promoted the proliferation of MSCs and increased the cellular half-life in vivo, but also improve their immune-modulating functions. The tube formation assay indicates that the MSCs could significantly pro-mote angiopoiesis. Moreover, the MSCs-laden hydrogel could inhibit fibrosis by modulating the synthesis of collagen and ameliorate disease progression in SSc disease model mice after subcutaneous injection of bleo-mycin. All these results highlight this novel MSCs-laden hydrogel and its distinctive functions in treatment of chronic SSc, indicating the additional potential to be used widely in the clinic.展开更多
Systemic sclerosis(SSc)is characterized by immune dysfunction,vasculopathy,chronic fibrosis of skin and internal organs with complex etiology.With the rapid development and the application in biomedicine of epigenetic...Systemic sclerosis(SSc)is characterized by immune dysfunction,vasculopathy,chronic fibrosis of skin and internal organs with complex etiology.With the rapid development and the application in biomedicine of epigenetics,accumulating evidence has shown that epigenetics plays an important role in the pathogenesis of SSc.Environmental factors via epigenetics are needed to trigger and maintain for the disease in the subjects with genetic predisposition to SSc.The role of epigenetics in the pathogenesis of SSc includes hypermethylation of the promoter region of nitric oxide synthase and bone morphogenetic protein receptors II,up-regulation of histone deacetylases 4 and 5 expression,and down-regulation of miR-193b and miR-152 in endothelial cells inducing vascular dysfunction;DNA hypermethylation and hypoacetylation of histone H3 and H4 in Friend leukemia virus integration 1 and Kruppel-like factor 5 genes,and the abnormal expression of miR-29,miR-129-5p and miR-135b in fibroblasts causing excessive fibrosis;DNA hypomethylation in the promoter regions of CD11a and CD70 genes in CD4+T cells resulting in immune dysfunction.Studies on the role of epigenetics in SSc are of great significance for better understanding the pathogenic machanism of SSc,which is helpful to find new molecular targets for treating SSc,and consequently,improve the prognosis of SSc.展开更多
Background:Systemic sclerosis is characterized by the involvement of organs and the presence of specific antibodies.The objectives of this study were to identify the autoantibodies and to determine their association w...Background:Systemic sclerosis is characterized by the involvement of organs and the presence of specific antibodies.The objectives of this study were to identify the autoantibodies and to determine their association with the selected clinical features of the disease among Bangladeshi systemic sclerosis patients.Methods:This cross-sectional study was performed at the rheumatology outpatient clinic of Bangabandhu Sheikh Mujib Medical University.Autoantibodies against nine systemic sclerosis-specific antigens were tested using an enzyme-linked immunoassay immunoblot kit.Several clinical features of patients with positive and negative autoantibody were examined by χ^(2) or Fisher's exact tests.Results:A total of 71 patients with systemic sclerosis(66;93.0%female)were included.Their mean age at disease onset was 33.2 years.Fifty-seven(80.3%)patients had diffuse cutaneous subtype.Out of nine autoantibodies,four were positive,anti-topoisomerase-I(57.7%),anti-U1 ribonucleic protein(21.1%),anti-RNA polymerase Ⅲ(18.3%),and anticentromere antibodies(4.2%).Eleven(15.5%)patients were negative for any antibodies and 11 patients were positive for at least two autoantibodies.Anti-U3-RNP,anti-PMScl,anti-Ku,and anti-Th/To auto antibodies were absent in all patients.Anti-RNA polymerase III was associated with raised pulmonary arterial systolic pressure(PASP)and anti-U1-RNP with decreased forced vital capacity(FVC).Conclusions:Anti-topoisomerase-I was the commonest autoantibody in patients with systemic sclerosis in Bangladesh.Anti-RNA polymerase III antibody had significant association with raised PASP and anti-U1-RNP with decreased FVC.展开更多
The relationship between infection and autoimmunity has been increasingly defined over the last 20 years. The systemic rheumatic diseases are characterized by dysregulation of the immune system resulting in a loss of ...The relationship between infection and autoimmunity has been increasingly defined over the last 20 years. The systemic rheumatic diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to self-antigen. The exact etiology for the majority of these diseases is unknown; however, a complex combination of host and environmental factors are believed to play a pivotal role. Helicobacter pylori(H. pylori) is one of the most widely studied infectious agents proposed as agents triggering autoimmune response. The persistent presence of H. pylori in the gastric mucosa results in chronic immune system activation with ongoing cytokine signaling, infiltration of gastric mucosa by neutrophils, macrophages, lymphocytes, as well as production of antibodies and effector T-cells. Various mechanisms have been proposed in an attempt to explain the extra-intestinal manifestations of H. pylori infections. These include: molecular mimicry, endothelial cell damage, superantigens and microchimerism. I performed a systematic literature review using the keywords "rheumatoid arthritis", "Sjgren's syndrome", "systemic sclerosis", "systemic lupus erythematosus","Helicobacter pylori " and "pathogenesis". A systematic literature search was carried out in MEDLINE; EMBASE; Cochrane Library and ACR/EULAR meeting abstracts. In systemic rheumatic diseases H. pylori infection prevalence alone should not be expected to provide sufficient evidence for or against a pathologic role in the disease. In this article Ⅰ review studies examining the potential involvement of H. pylori infection in autoimmune systemic rheumatic diseases. Further studies of the immunological response to H. pylori and its role in the pathogenesis of systemic rheumatic diseases are warranted.展开更多
Interleukin-2(IL-2)is an important cytokine that plays a key role in the immune response.The IL-2 receptor(IL-2R)is composed of three subunits,alpha,beta,and gamma,with the alpha subunit having the highest affinity fo...Interleukin-2(IL-2)is an important cytokine that plays a key role in the immune response.The IL-2 receptor(IL-2R)is composed of three subunits,alpha,beta,and gamma,with the alpha subunit having the highest affinity for IL-2.Several studies reported that immune dysregulation of IL-2 may cause tissue injury as well as damage leading to the pathogenesis of various autoimmune diseases such as acute necrotizing vasculitis in systemic lupus erythematosus(SLE),inflammatory synovitis in rheumatoid arthritis(RA),salivary and lacrimal gland dysfunction in Sjogren syndrome(SS),obliterative vasculopathy fibrosis in systemic sclerosis(SSc),and inflammatory demyelination in multiple sclerosis(MS).The aim of this review paper was to examine the role of IL-2/IL-2R in various autoimmune disorders,taking into account recent advancements and discoveries,gaps in the current literature,ongoing debates,and potential avenues for future research.The focus of this review is on systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,sjogren syndrome,and multiple sclerosis,which are all linked to the malfunctioning of IL-2/IL-2R.In genetic studies,gene polymorphisms of IL-2 such as IL-2330/T,IL-2330/G,and rs2069763 are involved in increasing the risk of SLE.Furthermore,genetic associations of IL-2/IL-2R such as rs791588,rs2281089,rs2104286,rs11594656,and rs35285258 are significantly associated with RA susceptibility.The IL-2 polymorphism including rs2069762A,rs6822844T,rs6835457G,and rs907715T are significant connections with systemic sclerosis.In addition,rs2104286(IL-2),rs11594656(IL-2RA),rs35285258(IL-2RB)gene polymorphism significant increases the risk of multiple sclerosis.In therapeutic approaches,low-dose IL-2 therapy could regulate Tfr and Tfh cells,resulting in a reduction in disease activity in the SLE patients.In addition,elevated sIL-2R levels in the peripheral blood of SLE patients could be linked to an immunoregulatory imbalance,which may contribute to the onset and progression of SLE.Consequently,sIL-2R could potentially be a target for future SLE therapy.Moreover,Low dose-IL2 was well-tolerated,and low levels of Treg and high levels of IL-21 wereassociated with positive responses to Ld-IL2 suggested to be a safe and effective treatment for RA.Additionally,low-dose IL-2 treatment improves the exocrine glands'ability to secrete saliva in SS-affected mice.Whereas,Basiliximab targets the alpha chain of the IL-2 receptor suggested as a potential treatment for SSc.Also,pre-andpost-treatment with Tregs,MDSCs,and IL-2 may have the potential to prevent EAE induction in patients with MS.It is suggested that further studies should be conducted on IL-2 polymorphism in Sjogren syndrome.展开更多
Background:Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin and organs,marked changes in microvascular structure,cellular and humoral immune disorders.Renal involvement is more f...Background:Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin and organs,marked changes in microvascular structure,cellular and humoral immune disorders.Renal involvement is more frequent and mainly characterized by moderate proteinuria,elevated serum creatinine levels,and hypertension.The most common kidney involvement in SSc is scleroderma renal crisis(SRC)that is fatal without prompt intervention.Case report:A 52-year-old Caucasian male with known diffuse cutaneous systemic sclerosis was hospitalized with communityacquired pneumonia.On the fifth day after appropriate antibiotic therapy and 60 mg/day methylprednisolone,decreased urine output,arterial hypertension,decreased renal function and pulmonary edema developed.The patient was diagnosed with a scleroderma renal crisis.Emergency hemodialysis was applied to the patient,and captopril 6×25 mg/day and nifedipine 2*60 mg/day treatment were given.He received a routine hemodialysis program for about three months.The hemodialysis program was terminated when the patient’s urine quality and quantity increased.Conclusions:SRC,characterized by malignant hypertension,azotemia,microangiopathic hemolytic anemia,and kidney failure,is one of the most important complications of systemic sclerosis with a poor prognosis without prompt intervention.Steroid use is one of the important risk factors that precipitate SRC development.With angiotensin-converting enzyme inhibitors,survival increased after SRC,the need for dialysis decreased,and usually allowed the discontinuation of dialysis treatment within about 6-18 months.Suspicion of SRC in the presence of the above-mentioned findings in patients with a diagnosis or suspected systemic sclerosis can be considered the most important treatment step.展开更多
The esophagus is the most commonly affected part of the gastrointestinal system in patients with systemic sclerosis(SSc).Esophageal involvement may lead to a significant reduction in patient quality of life.The exact ...The esophagus is the most commonly affected part of the gastrointestinal system in patients with systemic sclerosis(SSc).Esophageal involvement may lead to a significant reduction in patient quality of life.The exact pathophysiology is complex and not yet fully elucidated.Ultimately,esophageal smooth muscle becomes atrophied and replaced by fibrous tissue leading to severe motility disturbance of the distal esophagus.Symptoms are mainly attributed to gastroesophageal reflux disease and to esophageal dysmotility.Compelling evidence has correlated esophageal involvement to the severity of pulmonary disease.No formed guidelines exist about the diagnostic modalities used to assess esophageal disease in patients with SSc,though upper gastrointestinal endoscopy is the first and most important modality used as it can reveal alterations commonly observed in patients with SSc.Further exploration can be made by high resolution manometry and pH-impedance study.Proton pump inhibitors remain the mainstay of treatment,while prokinetic agents are commonly used as add-on therapy in patients with symptoms attributed to gastroesophageal reflux disease not responding to standard therapy as well as to motility disturbances.Gastroesophageal reflux disease symptoms in patients with SSc are frequently difficult to manage,and new therapeutic modalities are emerging.The role of surgical treatment is restricted and should only be preserved for resistant cases.展开更多
Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement,commonly in the esophagus.Dysphagia is a common clinical manifestation of systemic sclerosis and is strongl...Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement,commonly in the esophagus.Dysphagia is a common clinical manifestation of systemic sclerosis and is strongly related to esophageal dysmotility.However,there are multiple other contributing factors in each step in the physiology of swallowing that may contribute to development of severe dysphagia.The oral phase of swallowing may be disrupted by poor mastication due to microstomia and poor dentition,as well as by xerostomia.In the pharyngeal phase of swallowing,pharyngeal muscle weakness due to concurrent myositis or cricopharyngeal muscle tightening due to acid reflux can cause disturbance.The esophageal phase of swallowing is most commonly disturbed by decreased peristalsis and esophageal dysmotility.However,it can also be affected by obstruction from chronic reflux changes,pill-induced esophagitis,or Candida esophagitis.Other contributing factors to dysphagia include difficulties in food preparation and gastroparesis.Understanding the anatomy and physiology of swallowing and evaluating systemic sclerosis patients presenting with dysphagia for disturbances in each step can allow for development of better treatment plans to improve dysphagia and overall quality of life.展开更多
The increased awareness of systemic sclerosis(SS)and its pathogenetic background made the management of this disease more amenable than previously thought.However,scleroderma renal crisis(SRC)is a rarely seen as an as...The increased awareness of systemic sclerosis(SS)and its pathogenetic background made the management of this disease more amenable than previously thought.However,scleroderma renal crisis(SRC)is a rarely seen as an associated disorder that may involve 2%-15%of SS patients.Patients presented with earlier,rapidly progressing,diffuse cutaneous SS disease,mostly in the first 3-5 years after non-Raynaud clinical manifestations,are more vulnerable to develop SRC.SRC comprises a collection of acute,mostly symptomatic rise in blood pressure,elevation in serum creatinine concentrations,oliguria and thrombotic microangiopathy in almost 50%of cases.The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis.In a scleroderma patient maintained on regular dialysis;every effort should be exerted to declare any possible evidence of renal recovery.A given period of almost two years has been suggested prior to proceeding in a kidney transplant(KTx).Of note,SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease(ESRD).KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients.Compared to other primary renal diseases,SS-related ESRD was considered for a long period of poor patient and allograft survivals.Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death.Recurrence of SRC after transplantation has been observed in some patients.However,an excellent post-transplant patient and graft outcome have been recently reported.Consequently,the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.展开更多
This report describes clinical findings of a 28-year old female patient presented with non-healing digit ulcer and Raynaud’s phenomenon. Upon investigation was found to have high eosinophil count alongside hypocomple...This report describes clinical findings of a 28-year old female patient presented with non-healing digit ulcer and Raynaud’s phenomenon. Upon investigation was found to have high eosinophil count alongside hypocomplementemia. This patient was diagnosed with diffuse cutaneous systemic sclerosis and was started on therapy;her other laboratory findings were attributed to a coinciding helminthic infection. This case suggests the possibility of having two different diagnoses presenting at once causing a clinical dilemma.展开更多
基金National Natural Science Foundation of China(No.8186029481860295)Natural Science Foundation of Inner Mongolia Autonomous Region(No.2019MS080552021MS08045)Science and Technology Plan Project of Inner Mongolia Autonomous Region(No.2018020892019GG052)。
文摘Objective: This study was to investigate the role of hsa-miR-155-3p and hsa-miR-155-5p as biomarkers and regulators of biological behavior in Systemic Sclerosis. Methods: A total of 10 SSc patients and 10 healthy controls were selected for the study. The expression levels of hsa-miR-155-3p and hsa-miR-155-5p in peripheral blood mononuclear cells of SSc patients and healthy controls were measured using RT-qPCR. The diagnostic value of these miRNAs was explored using Receiver Operating Characteristic curve analysis. Pearson or Spearman correlation analysis was performed to assess the correlation between miRNAs and clinical indicators in SSc patients. Potential target genes of hsa-miR-155-3p and hsa-miR-155-5p were predicted using miRDB, Targetscan, and miRDIP databases. GO functional annotation, KEGG pathway enrichment analysis, protein-protein interaction network construction, and selection of central genes were conducted. Results: The expression levels of hsa-miR-155-3p and hsa- miR-155-5p were significantly higher in PBMCs of SSc patients compared to healthy controls (P<0.001). The ROC curve analysis showed that hsa-miR-155-3p and hsa-miR-155-5p had a high diagnostic value for SSc (AUC=1, P<0.001). Correlation analysis revealed that hsa- miR-155-3p, hsa-miR-155-5p, and clinical indicators such as high-resolution CT, neutrophil percentage, lymphocyte percentage, and albumin to globulin ratio were correlated (P<0.05). The signaling pathways enriched with target genes of hsa-miR-155-3p and hsa-miR-155- 5p were closely associated with the occurrence and development of SSc fibrosis, immunity, and inflammation. Conclusions: hsa-miR-155-3p and hsa-miR-155-5p may be involved in regulating the occurrence and development of SSc fibrosis, immunity, and inflammation. They have the potential to serve as biomarkers for clinical diagnosis and treatment of SSc.
文摘Scleroderma is a rare disease with two primary forms: localized scleroderma (LS) and systemic sclerosis (SSc). Both are chronic conditions that can manifest in various patterns (subtypes) and are linked to extracutaneous involvement in pediatric patients. Juvenile SSc poses a higher risk of morbidity and mortality, with patients facing life-threatening complications such as lung, heart, and visceral organ fibrosis, and vasculopathy. In contrast, mortality is extremely rare in juvenile LS, but patients are susceptible to significant morbidity, leading to severe disfigurement and functional impairment. Treatment for scleroderma aims to control inflammation and address specific issues. An early diagnosis significantly enhances the overall outcome. This study conducts a retrospective descriptive analysis aiming to document the clinical manifestations, management approaches, and outcomes of systemic sclerosis in a cohort of nine children receiving treatment for juvenile systemic sclerosis at Pediatric B department of Mohammed VI University, Hospital Center in Marrakech, Morocco.
文摘Adipose-derived stem cells(ADSCs)residing in the stromal vascular fraction(SVF)of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis(SSc),a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular lesions.Several preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous manifestations of SSc patients.However,currently available data indicate that ADSCs may represent a double-edged sword in SSc,as they may exhibit a pro-fibrotic and anti-adipogenic phenotype,possibly behaving as an additional pathogenic source of pro-fibrotic myofibroblasts through the adipocyte-to-myofibroblast transition process.Thus,in the perspective of a larger employ of SSc-ADSCs for further therapeutic applications,it is important to definitely unravel whether these cells present a comparable phenotype and similar immunosuppressive,anti-inflammatory,anti-fibrotic and pro-angiogenic properties in respect to healthy ADSCs.In light of the dual role that ADSCs seem to play in SSc,this review will provide a summary of the most recent insights into the preclinical and clinical studies employing SVF and ADSCs for the treatment of the disease and,at the same time,will focus on the main findings highlighting the possible involvement of these stem cells in SSc-related fibrosis pathogenesis.
文摘Systemic sclerosis is an autoimmune disease characterized by vascular disease,fibrosis of the skin,and internal organ dysfunction.Gastrointestinal involvement is the most frequent complication of internal organs,impacting up to 90%of patients.Gastrointestinal involvement can affect any region of the gastrointestinal tract from the mouth to the anus,with a predominance of disorders being observed at the level of the upper digestive tract.The gastrointestinal involvement primarily involves the esophagus,small bowel,and rectum.The severity of gastrointestinal involvement affects quality of life and is a marker of worse prognosis and mortality in these patients.In this review,we describe the current findings regarding gastrointestinal involvement by this entity.
文摘Background:To explore the relevant targets of the Chinese herbal medicine compound Danggui-Sini Decoction(DGSND)for the treatment of systemic sclerosis(SSc).Method:We used TCMSP to enlist ingredients and Swiss Target Prediction for targets fishing,and the protein names by UniProt for organized as gene symbol.Strawberry Perl was used to integrate the active ingredients and the drugs action target of DGSND,with Cytoscape 3.9.0 software to construct"Active ingredient-Drug target"network.Then,GEO database,GeneCards database,TTDdatabase,DisGENent database and MalaCards database for SSc-related disease target prediction,and then analyzed the active drug targets of DGSND and SSc-related targets of Danggui-Sini Decoction treat SSc.Then,the above results we combined with STRING database to visualize the Protein-protein interaction(PPI)network for the core targets of SSc,and performed Gene ontology(GO)functional analysis and Kyoto Encyclopedia of Genomics(KEGG)signaling pathway enrichment analysis for SSc-related targets treated with DGSND Result:DGSND contains 223 active ingredients including Sitogluside,Benzoylpaeoniflorin,(-)-Asarinin Palbinone,Glycyro,4'DMEP etc.which acts on Signal transducer and activator of transcription 3(STAT3),Tumor Necrosis Factor(TNF),Vascular endothelial growth factor(VEGFA),Nuclear factor kappa-B(NFκB1),Interleukin(IL1β,IL17),Mitogen-activated protein kinase(MAPK)and Janus Kinase(JAK)and many other genes totaling 176,mainly involved in 4 more biological processes 3 molecular functions and 3 cellular components.Conclusion:DGSND is primarily used to treat SSc by regulating calcium homeostasis,inflammatory signaling pathways and neural cell repair and apoptosis-related pathways within the body.
基金National Natural Science Foundation of China(No.81774300)National Natural Science Foundation of China-Henan Joint Fund Project(No.U1704191)。
文摘Objective:To explore the molecular mechanism of Capparis spinosa in the treatment of systemic sclerosis((SSC))based on network pharmacology.Methods:GEO,Genecards,Pharmgkb,TTD and Drugbank databases were used to obtain SSC targets,related literatures and Swisstargetprediction databases were used to obtain the main components of Citrus and their corresponding targets,and intersection was used to obtain prediction targets.Log in to the String database to analyze the protein interaction of the prediction target(PPI),further used Cytoscape to obtain the core gene by network topology analysis,and the core gene was docked with the main components of Capparis spinosa.The prediction targets were analyzed by gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis using R software.Results:A total of 15 active components and their targets were obtained,3171 SSC targets were obtained,and 66 predicted targets were obtained by intersection.Ten PPI core genes such as VEGFA,TNF,AKT1,PTGS2 and MMP9 were obtained by topological analysis.GO analysis involved many biological processes such as reactive oxygen species metabolic process、protein kinase B signaling、regulation of inflammatory response、phosphatidylinositol 3-kinase signaling and so on.KEGG pathway analysis showed PI3K-Akt signaling pathway,Proteoglycans in cancer,Focal adhesion,Rap1 signaling pathway and other signaling pathways.Conclusion:The molecular mechanism of Capparis spinosa in the treatment of SSC is predicted by the method of network pharmacology,which provides theoretical basis and data support for the basic research of Citrus officinalis in the treatment of SSC.
文摘Introduction: Cutaneous manifestations of systemic sclerosis (SSc) include skin ulceration;4% - 12% of patients with SSc develop lower extremity ulcers of various etiologies. Limited data, significant morbidity, and substantial cost of wound care led us to undertake this study to describe and identify risk factors. Methods: After Institutional Review Board approval, we identified 30 patients with SSc and lower extremity ulcers over a 10-year period at a single center with an SSc clinic, which were included in a descriptive analysis. Results: Median age of onset of lower extremity ulcers was 59.5 years (range 20 - 84). Ninety percent of patients were female, 60% were Caucasian, 63% had limited SSc, 13% diffuse SSc and 23% an overlap syndrome. Immunomodulators or steroids were prescribed in 53%;hypercoagulable state identified in 16%. Ulcers were attributed to venous stasis (27%), SSc (20%), trauma (20%), arterial disease (17%), and multifactorial/unknown (17%). In patients with ulcers attributed to SSc, age at onset was lower (45.5 vs 59.5 years). Biopsies generally did not contribute to management. Multidisciplinary treatment was routine;20% required amputation, 10% endovascular intervention, 20% frequent surgical debridement, 10% hyperbaric oxygen, 26% local treatment and antibiotics and 13% received immunosuppression for wound treatment. Conclusion: Lower extremity ulcers are a serious clinical problem in patients with SSc. The clinical exam, venous dopplers, ankle-brachial indices and assessment of vascular risk factors helped define causality. In younger patients, ulcers were more frequently attributed to SSc and these patients were more likely to be on immunosuppressants/DMARDS, possibly indicating severe phenotype of SSc.
文摘Background:There is a dearth of mortality data on systemic sclerosis(SSc)in sub-Saharan Africa.We undertook a retrospective study of causes and predictors of death in low-income indigent South Africans with SSc.Methods:A retrospective records review of clinicodemographic,laboratory,and outcome data of SSc patients attending a state-funded tertiary Rheumatology service in South Africa.Results:Most of the 164 patients were Black(92.7%)and female(87.8%).The mean(SD)age at diagnosis and follow-up duration were 42.6(12.9)and 5.5(5.6)years,respectively.The majority(75.6%)had diffuse cutaneous SSc(dcSSc);and digital pits/ulcers,interstitial lung disease(ILD),and pulmonary hypertension(PH)were documented in 73.6%,55.0%,and 38.3%,respectively.There were 56 known deaths and an equal number of patients were lost to follow-up.Deaths resulted from ILD complicated by PH(42.9%),infections(8.9%),cardiac disease(7.1%),and malignancies(3.6%).Estimated 5-and 10-year survival rates for patients with known outcomes were 58%and 42%,respectively.Independent predictors of death were renal dysfunction and cor pulmonale.Conclusion:Most patients in this study of South Africans had dcSSc and poor outcomes.Known deaths resulted from cardiorespiratory complications of ILD complicated by PH.Cor pulmonale and renal dysfunction were independent predictors of death.
基金Supported by the Administration of Traditional Chinese Medicine of Gansu Province in China(No.GZK-2012-66)
文摘Objective:To examine the efficacy and safety of bathing therapy with Taohong Siwu Decoction(桃红四物汤,TSD) in the treatment of early-stage,mild-moderate diffuse cutaneous systemic sclerosis(dc SSc).Methods:This randomized,placebo-controlled trial enrolled 148 men and women(18–60 years) with dc SSc(disease duration 12 months) and baseline modified Rodnan skin score(MRSS) 10.Patients were randomized into a TSD group(71 cases bathing with TSD plus oral prednisone) or control group(71 cases bathing with placebo plus oral prednisone).Bathing(40 ℃,30 min) of the upper and lower limbs was carried out once daily for 12 consecutive weeks.The primary outcome measure was MRSS;secondary outcomes were Raynaud's phenomenon(RP) score,quality of life(QOL),physician visual analogue scale(VAS),patient VAS,percent predicted diffusing capacity for carbon monoxide(DLCO),percent predicted forced vital capacity(FVC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP) level and overall treatment effect.Results:The final analysis included 135 patients(control group,68 cases;TSD group,67 cases).Primary and secondary outcome measures after 2 weeks of treatment showed no improvement(versus baseline) in both groups,with no differences between groups.At 12 weeks,QOL,physician VAS,patient VAS,ESR and CRP were improved in both groups,but MRSS and RP score were improved only in the TSD group(all P<0.05).MRSS,RP score,QOL,physician VAS,patient VAS,ESR and CRP differed significantly between groups(all P<0.05).Meanwhile,the overall treatment effect was significantly higher in the TSD group than in the control group(P<0.05).Adverse events in the two groups were similar(P>0.05).Conclusions:Bathing with TSD plus oral prednisone achieves better outcomes than oral prednisone alone in patients with dcS Sc and is not associated with serious adverse events.
文摘Systemic sclerosis is a rare chronic autoimmune disease with extensive microvascular injury, damage of endothelialcells, activation of immune responses, and progression of tissue fibrosis in the skin and various internal organs.According to epidemiological data, women’s populations are more susceptible to systemic sclerosis than men. Untilnow, various therapeutic options are employed to manage the symptoms of the disease. Since stem cell-basedtreatments have developed as a novel approach to rescue from several autoimmune diseases, it seems that stemcells, especially mesenchymal stem cells as a powerful regenerative tool can also be advantageous for systemicsclerosis treatment via their remarkable properties including immunomodulatory and anti-fibrotic effects.Accordingly, we discuss the contemporary status and future perspectives of mesenchymal stem cell transplantationfor systemic sclerosis.
基金This work was supported by National Key Research and Develop-ment Program of China Stem Cell and Translational Research(2020YFA0710800)National Natural Science Foundation of China(grant no.81930043)+2 种基金Major International Joint Research Project of China(grant no.81720108020)National Natural Science Foundation of China(grant no.82001721)Jiangsu Provincial Key Research and Development Program(BE2020621).
文摘As a novel cellular therapy, the anti-inflammatory and immunomodulatory virtues of mesenchymal stem cells (MSCs) make them promising candidates for systemic sclerosis (SSc) treatment. However, the clinical efficacy of this stratagem is limited because of the short persistence time, poor survival, and engraftment of MSCs after injection in vivo. Herein, we develop a novel MSCs-laden injectable self-healing hydrogel for SSc treatment. The hydrogel is prepared using N, O-carboxymethyl chitosan (CS-CM) and 4-armed benzaldehyde-terminated poly-ethylene glycol (PEG-BA) as the main components, imparting with self-healing capacity via the reversible Schiff-base connection between the amino and benzaldehyde groups. We demonstrate that the hydrogel laden with MSCs not only promoted the proliferation of MSCs and increased the cellular half-life in vivo, but also improve their immune-modulating functions. The tube formation assay indicates that the MSCs could significantly pro-mote angiopoiesis. Moreover, the MSCs-laden hydrogel could inhibit fibrosis by modulating the synthesis of collagen and ameliorate disease progression in SSc disease model mice after subcutaneous injection of bleo-mycin. All these results highlight this novel MSCs-laden hydrogel and its distinctive functions in treatment of chronic SSc, indicating the additional potential to be used widely in the clinic.
文摘Systemic sclerosis(SSc)is characterized by immune dysfunction,vasculopathy,chronic fibrosis of skin and internal organs with complex etiology.With the rapid development and the application in biomedicine of epigenetics,accumulating evidence has shown that epigenetics plays an important role in the pathogenesis of SSc.Environmental factors via epigenetics are needed to trigger and maintain for the disease in the subjects with genetic predisposition to SSc.The role of epigenetics in the pathogenesis of SSc includes hypermethylation of the promoter region of nitric oxide synthase and bone morphogenetic protein receptors II,up-regulation of histone deacetylases 4 and 5 expression,and down-regulation of miR-193b and miR-152 in endothelial cells inducing vascular dysfunction;DNA hypermethylation and hypoacetylation of histone H3 and H4 in Friend leukemia virus integration 1 and Kruppel-like factor 5 genes,and the abnormal expression of miR-29,miR-129-5p and miR-135b in fibroblasts causing excessive fibrosis;DNA hypomethylation in the promoter regions of CD11a and CD70 genes in CD4+T cells resulting in immune dysfunction.Studies on the role of epigenetics in SSc are of great significance for better understanding the pathogenic machanism of SSc,which is helpful to find new molecular targets for treating SSc,and consequently,improve the prognosis of SSc.
文摘Background:Systemic sclerosis is characterized by the involvement of organs and the presence of specific antibodies.The objectives of this study were to identify the autoantibodies and to determine their association with the selected clinical features of the disease among Bangladeshi systemic sclerosis patients.Methods:This cross-sectional study was performed at the rheumatology outpatient clinic of Bangabandhu Sheikh Mujib Medical University.Autoantibodies against nine systemic sclerosis-specific antigens were tested using an enzyme-linked immunoassay immunoblot kit.Several clinical features of patients with positive and negative autoantibody were examined by χ^(2) or Fisher's exact tests.Results:A total of 71 patients with systemic sclerosis(66;93.0%female)were included.Their mean age at disease onset was 33.2 years.Fifty-seven(80.3%)patients had diffuse cutaneous subtype.Out of nine autoantibodies,four were positive,anti-topoisomerase-I(57.7%),anti-U1 ribonucleic protein(21.1%),anti-RNA polymerase Ⅲ(18.3%),and anticentromere antibodies(4.2%).Eleven(15.5%)patients were negative for any antibodies and 11 patients were positive for at least two autoantibodies.Anti-U3-RNP,anti-PMScl,anti-Ku,and anti-Th/To auto antibodies were absent in all patients.Anti-RNA polymerase III was associated with raised pulmonary arterial systolic pressure(PASP)and anti-U1-RNP with decreased forced vital capacity(FVC).Conclusions:Anti-topoisomerase-I was the commonest autoantibody in patients with systemic sclerosis in Bangladesh.Anti-RNA polymerase III antibody had significant association with raised PASP and anti-U1-RNP with decreased FVC.
文摘The relationship between infection and autoimmunity has been increasingly defined over the last 20 years. The systemic rheumatic diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to self-antigen. The exact etiology for the majority of these diseases is unknown; however, a complex combination of host and environmental factors are believed to play a pivotal role. Helicobacter pylori(H. pylori) is one of the most widely studied infectious agents proposed as agents triggering autoimmune response. The persistent presence of H. pylori in the gastric mucosa results in chronic immune system activation with ongoing cytokine signaling, infiltration of gastric mucosa by neutrophils, macrophages, lymphocytes, as well as production of antibodies and effector T-cells. Various mechanisms have been proposed in an attempt to explain the extra-intestinal manifestations of H. pylori infections. These include: molecular mimicry, endothelial cell damage, superantigens and microchimerism. I performed a systematic literature review using the keywords "rheumatoid arthritis", "Sjgren's syndrome", "systemic sclerosis", "systemic lupus erythematosus","Helicobacter pylori " and "pathogenesis". A systematic literature search was carried out in MEDLINE; EMBASE; Cochrane Library and ACR/EULAR meeting abstracts. In systemic rheumatic diseases H. pylori infection prevalence alone should not be expected to provide sufficient evidence for or against a pathologic role in the disease. In this article Ⅰ review studies examining the potential involvement of H. pylori infection in autoimmune systemic rheumatic diseases. Further studies of the immunological response to H. pylori and its role in the pathogenesis of systemic rheumatic diseases are warranted.
文摘Interleukin-2(IL-2)is an important cytokine that plays a key role in the immune response.The IL-2 receptor(IL-2R)is composed of three subunits,alpha,beta,and gamma,with the alpha subunit having the highest affinity for IL-2.Several studies reported that immune dysregulation of IL-2 may cause tissue injury as well as damage leading to the pathogenesis of various autoimmune diseases such as acute necrotizing vasculitis in systemic lupus erythematosus(SLE),inflammatory synovitis in rheumatoid arthritis(RA),salivary and lacrimal gland dysfunction in Sjogren syndrome(SS),obliterative vasculopathy fibrosis in systemic sclerosis(SSc),and inflammatory demyelination in multiple sclerosis(MS).The aim of this review paper was to examine the role of IL-2/IL-2R in various autoimmune disorders,taking into account recent advancements and discoveries,gaps in the current literature,ongoing debates,and potential avenues for future research.The focus of this review is on systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,sjogren syndrome,and multiple sclerosis,which are all linked to the malfunctioning of IL-2/IL-2R.In genetic studies,gene polymorphisms of IL-2 such as IL-2330/T,IL-2330/G,and rs2069763 are involved in increasing the risk of SLE.Furthermore,genetic associations of IL-2/IL-2R such as rs791588,rs2281089,rs2104286,rs11594656,and rs35285258 are significantly associated with RA susceptibility.The IL-2 polymorphism including rs2069762A,rs6822844T,rs6835457G,and rs907715T are significant connections with systemic sclerosis.In addition,rs2104286(IL-2),rs11594656(IL-2RA),rs35285258(IL-2RB)gene polymorphism significant increases the risk of multiple sclerosis.In therapeutic approaches,low-dose IL-2 therapy could regulate Tfr and Tfh cells,resulting in a reduction in disease activity in the SLE patients.In addition,elevated sIL-2R levels in the peripheral blood of SLE patients could be linked to an immunoregulatory imbalance,which may contribute to the onset and progression of SLE.Consequently,sIL-2R could potentially be a target for future SLE therapy.Moreover,Low dose-IL2 was well-tolerated,and low levels of Treg and high levels of IL-21 wereassociated with positive responses to Ld-IL2 suggested to be a safe and effective treatment for RA.Additionally,low-dose IL-2 treatment improves the exocrine glands'ability to secrete saliva in SS-affected mice.Whereas,Basiliximab targets the alpha chain of the IL-2 receptor suggested as a potential treatment for SSc.Also,pre-andpost-treatment with Tregs,MDSCs,and IL-2 may have the potential to prevent EAE induction in patients with MS.It is suggested that further studies should be conducted on IL-2 polymorphism in Sjogren syndrome.
文摘Background:Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin and organs,marked changes in microvascular structure,cellular and humoral immune disorders.Renal involvement is more frequent and mainly characterized by moderate proteinuria,elevated serum creatinine levels,and hypertension.The most common kidney involvement in SSc is scleroderma renal crisis(SRC)that is fatal without prompt intervention.Case report:A 52-year-old Caucasian male with known diffuse cutaneous systemic sclerosis was hospitalized with communityacquired pneumonia.On the fifth day after appropriate antibiotic therapy and 60 mg/day methylprednisolone,decreased urine output,arterial hypertension,decreased renal function and pulmonary edema developed.The patient was diagnosed with a scleroderma renal crisis.Emergency hemodialysis was applied to the patient,and captopril 6×25 mg/day and nifedipine 2*60 mg/day treatment were given.He received a routine hemodialysis program for about three months.The hemodialysis program was terminated when the patient’s urine quality and quantity increased.Conclusions:SRC,characterized by malignant hypertension,azotemia,microangiopathic hemolytic anemia,and kidney failure,is one of the most important complications of systemic sclerosis with a poor prognosis without prompt intervention.Steroid use is one of the important risk factors that precipitate SRC development.With angiotensin-converting enzyme inhibitors,survival increased after SRC,the need for dialysis decreased,and usually allowed the discontinuation of dialysis treatment within about 6-18 months.Suspicion of SRC in the presence of the above-mentioned findings in patients with a diagnosis or suspected systemic sclerosis can be considered the most important treatment step.
文摘The esophagus is the most commonly affected part of the gastrointestinal system in patients with systemic sclerosis(SSc).Esophageal involvement may lead to a significant reduction in patient quality of life.The exact pathophysiology is complex and not yet fully elucidated.Ultimately,esophageal smooth muscle becomes atrophied and replaced by fibrous tissue leading to severe motility disturbance of the distal esophagus.Symptoms are mainly attributed to gastroesophageal reflux disease and to esophageal dysmotility.Compelling evidence has correlated esophageal involvement to the severity of pulmonary disease.No formed guidelines exist about the diagnostic modalities used to assess esophageal disease in patients with SSc,though upper gastrointestinal endoscopy is the first and most important modality used as it can reveal alterations commonly observed in patients with SSc.Further exploration can be made by high resolution manometry and pH-impedance study.Proton pump inhibitors remain the mainstay of treatment,while prokinetic agents are commonly used as add-on therapy in patients with symptoms attributed to gastroesophageal reflux disease not responding to standard therapy as well as to motility disturbances.Gastroesophageal reflux disease symptoms in patients with SSc are frequently difficult to manage,and new therapeutic modalities are emerging.The role of surgical treatment is restricted and should only be preserved for resistant cases.
文摘Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement,commonly in the esophagus.Dysphagia is a common clinical manifestation of systemic sclerosis and is strongly related to esophageal dysmotility.However,there are multiple other contributing factors in each step in the physiology of swallowing that may contribute to development of severe dysphagia.The oral phase of swallowing may be disrupted by poor mastication due to microstomia and poor dentition,as well as by xerostomia.In the pharyngeal phase of swallowing,pharyngeal muscle weakness due to concurrent myositis or cricopharyngeal muscle tightening due to acid reflux can cause disturbance.The esophageal phase of swallowing is most commonly disturbed by decreased peristalsis and esophageal dysmotility.However,it can also be affected by obstruction from chronic reflux changes,pill-induced esophagitis,or Candida esophagitis.Other contributing factors to dysphagia include difficulties in food preparation and gastroparesis.Understanding the anatomy and physiology of swallowing and evaluating systemic sclerosis patients presenting with dysphagia for disturbances in each step can allow for development of better treatment plans to improve dysphagia and overall quality of life.
文摘The increased awareness of systemic sclerosis(SS)and its pathogenetic background made the management of this disease more amenable than previously thought.However,scleroderma renal crisis(SRC)is a rarely seen as an associated disorder that may involve 2%-15%of SS patients.Patients presented with earlier,rapidly progressing,diffuse cutaneous SS disease,mostly in the first 3-5 years after non-Raynaud clinical manifestations,are more vulnerable to develop SRC.SRC comprises a collection of acute,mostly symptomatic rise in blood pressure,elevation in serum creatinine concentrations,oliguria and thrombotic microangiopathy in almost 50%of cases.The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis.In a scleroderma patient maintained on regular dialysis;every effort should be exerted to declare any possible evidence of renal recovery.A given period of almost two years has been suggested prior to proceeding in a kidney transplant(KTx).Of note,SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease(ESRD).KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients.Compared to other primary renal diseases,SS-related ESRD was considered for a long period of poor patient and allograft survivals.Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death.Recurrence of SRC after transplantation has been observed in some patients.However,an excellent post-transplant patient and graft outcome have been recently reported.Consequently,the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.
文摘This report describes clinical findings of a 28-year old female patient presented with non-healing digit ulcer and Raynaud’s phenomenon. Upon investigation was found to have high eosinophil count alongside hypocomplementemia. This patient was diagnosed with diffuse cutaneous systemic sclerosis and was started on therapy;her other laboratory findings were attributed to a coinciding helminthic infection. This case suggests the possibility of having two different diagnoses presenting at once causing a clinical dilemma.
