BACKGROUND Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis(AP)but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surround...BACKGROUND Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis(AP)but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism.This non-pancreatic hyperlipasemia(NPHL)is puzzling for attending physicians during the diagnostic procedure for AP.It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it.A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.AIM To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease outcomes.METHODS A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal(ULN)was prospectively evaluated over 31 months.Patients were identified using daily electronic laboratory reports developed to support an ongoing observational,multicenter,prospective cohort study called the EASY trial(ISRCTN10525246)to establish a simple,easy,and accurate clinical scoring system for early prognostication of AP.Diagnosis of NPHL was established based on≥3×ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.RESULTS A total of 808 patients[male,n=420(52%);median age(IQR):65(51-75)years]were diagnosed with≥3×ULN serum lipase levels.A total of 392 patients had AP,whereas 401 had NPHL with more than 20 different etiologies.Sepsis and acute kidney injury(AKI)were the most prevalent etiologies of NPHL(27.7%and 33.2%,respectively).The best discriminative cut-off value for lipase was≥666 U/L(sensitivity,71.4%;specificity,88.8%).The presence of AKI or sepsis negatively affected the diagnostic performance of lipase.NPHL was associated with a higher in-hospital mortality than AP(22.4%vs 5.1%,P<0.001).In multivariate binary logistic regression,not lipase but increased amylase level(>244 U/L)and neutrophil-to-lymphocyte ratio(NLR)(>10.37,OR:3.71,95%CI:2.006-6.863,P<0.001),decreased albumin level,age,and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.CONCLUSION NPHL is a common cause of lipase elevation and is associated with high mortality rates.Increased NLR value was associated with the highest mortality risk.The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.展开更多
BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by th...BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.展开更多
Innate and adaptive immune dysfunction,also referred to as cirrhosis-associated immune dysfunction syndrome,is a major component of cirrhosis,and plays a pivotal role in the pathogenesis of both the acute and chronic ...Innate and adaptive immune dysfunction,also referred to as cirrhosis-associated immune dysfunction syndrome,is a major component of cirrhosis,and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function.During the evolution of the disease,acute decompensation events associated with organ failure(s),so-called acute-on chronic liver failure,and chronic decompensation with progression of liver fibrosis and also development of disease specific complications,comprise distinct clinical entities with different immunopathology mechanisms.Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations.Acute and chronic exposure to bacteria and/or their products,however,can result in variable clinical consequences.The immune status of patients is not constant during the illness;consequently,alterations of the balance between pro-and anti-in-flammatory processes result in very different dynamic courses.In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis.We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms.Moreover,we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease.Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications,delaying progression and reducing mortality.展开更多
AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 ...AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.展开更多
基金Supported by the Economic Development and Innovation Operative Program Grant,No.GINOP 2.3.2-15-2016-00048“StayAlive”Human Resources Development Operational Program Grant of the National Research Development and Innovation Office,No.EFOP-3.6.2-16-2017-00006.
文摘BACKGROUND Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis(AP)but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism.This non-pancreatic hyperlipasemia(NPHL)is puzzling for attending physicians during the diagnostic procedure for AP.It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it.A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.AIM To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease outcomes.METHODS A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal(ULN)was prospectively evaluated over 31 months.Patients were identified using daily electronic laboratory reports developed to support an ongoing observational,multicenter,prospective cohort study called the EASY trial(ISRCTN10525246)to establish a simple,easy,and accurate clinical scoring system for early prognostication of AP.Diagnosis of NPHL was established based on≥3×ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.RESULTS A total of 808 patients[male,n=420(52%);median age(IQR):65(51-75)years]were diagnosed with≥3×ULN serum lipase levels.A total of 392 patients had AP,whereas 401 had NPHL with more than 20 different etiologies.Sepsis and acute kidney injury(AKI)were the most prevalent etiologies of NPHL(27.7%and 33.2%,respectively).The best discriminative cut-off value for lipase was≥666 U/L(sensitivity,71.4%;specificity,88.8%).The presence of AKI or sepsis negatively affected the diagnostic performance of lipase.NPHL was associated with a higher in-hospital mortality than AP(22.4%vs 5.1%,P<0.001).In multivariate binary logistic regression,not lipase but increased amylase level(>244 U/L)and neutrophil-to-lymphocyte ratio(NLR)(>10.37,OR:3.71,95%CI:2.006-6.863,P<0.001),decreased albumin level,age,and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.CONCLUSION NPHL is a common cause of lipase elevation and is associated with high mortality rates.Increased NLR value was associated with the highest mortality risk.The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.
基金Supported by the German Federal Ministry of Education and Research(BMBF-Wachstumskern-PRAEMED.BIO),03WKDB2Csupported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,BO/00232/17/5+1 种基金Research Grants of National Research Development and Innovation Office,K115818/2015/1New National Excellence Program of the Ministry of Human Capacities,ÚNKP-18-4 Bolyai Plus.
文摘BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
基金Supported by Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences and Internal Research Grant of University of Debrecen
文摘Innate and adaptive immune dysfunction,also referred to as cirrhosis-associated immune dysfunction syndrome,is a major component of cirrhosis,and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function.During the evolution of the disease,acute decompensation events associated with organ failure(s),so-called acute-on chronic liver failure,and chronic decompensation with progression of liver fibrosis and also development of disease specific complications,comprise distinct clinical entities with different immunopathology mechanisms.Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations.Acute and chronic exposure to bacteria and/or their products,however,can result in variable clinical consequences.The immune status of patients is not constant during the illness;consequently,alterations of the balance between pro-and anti-in-flammatory processes result in very different dynamic courses.In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis.We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms.Moreover,we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease.Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications,delaying progression and reducing mortality.
基金Supported by Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,Internal Research Grant of University of Debrecen and the IOIBD Research Grant
文摘AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.
