AIM: To investigate reactivated Epstein-Barr virus (EBV) infection as a cause for chronic hepatitis. METHODS: Patients with occasionally established elevated serum aminotransferases were studied. HIV, HBV and HCV-infe...AIM: To investigate reactivated Epstein-Barr virus (EBV) infection as a cause for chronic hepatitis. METHODS: Patients with occasionally established elevated serum aminotransferases were studied. HIV, HBV and HCV-infections were excluded as well as any other immunosuppressive factors, metabolic or toxic disorders. EBV viral capsid antigen (VCA) IgG and IgM, EA-R and EA-D IgG and Epstein-Barr nuclear antigen (EBNA) were measured using IFA kits. Immunophenotyping of whole blood was performed by multicolor flow cytometry. CD8+ T cell responses to EBV and PHA were determined according to the intracellular expression of IFN-γ. RESULTS: The mean alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGTP) values exceeded twice the upper normal limit, AST/ALT ratio < 1. Serology tests showed reactivated EBV infection in all patients. Absolute number and percentages of T, B and NK cells were within the reference ranges. Fine subset analysis, in comparison to EBV+ healthy carriers, revealed a significant decrease of naive T cells (P < 0.001), accompanied by increased percentage of CD45RA- (P < 0.0001), and terminally differentiated CD28-CD27- CD8+ T cells (P < 0.01). Moderately elevated numbers of CD38 molecules on CD8+ T cells (P < 0.05) proposed a low viral burden. A significantly increased percentage of CD8+ T cells expressing IFN-γ in response to EBV and PHA stimulation was registered in patients, as compared to controls (P < 0.05). Liver biopsy specimens from 5 patients revealed nonspecific features of low-grade hepatitis.CONCLUSION: Chronic hepatitis might be a manifestation of chronic EBV infection in the lack of detectable immune deficiency; the expansion of CD28- CD27- and increase of functional EBV-specific CD8+ T cells being the only surrogate markers of viral activity.展开更多
Today the HIV infection is a chronic disease with significantly longer duration of the life of the patients. Problems of pressing interest are the persistent immune activation and chronic inflammation during the treat...Today the HIV infection is a chronic disease with significantly longer duration of the life of the patients. Problems of pressing interest are the persistent immune activation and chronic inflammation during the treatment with antiretroviral therapy. Taking this into account, different factors which could affect the immune system and the progress of the HIV infection are being researched. Vitamin D (25(OH)D) is one of those factors if we take note of its effect on the innate and acquired immunity. The aim of this study was to assess 25-hydroxyvitamin D (vitamin D) status in one part of the Bulgarian HIV-infected adult population and to assess connection between 25-hydroxyvitamin D (vitamin D) status and plasma levels of some major cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ). The study includes 145 HIV-positive patients, who are being monitored in the Department for acquired immune deficiency at Specialized Hospital for Infectious and Parasitic Diseases “Proff. Ivan Kirov”—Sofia. From all of the monitored patients only in 15% of the tested we found normal 25(OH)D serum levels, and in 12% of the patients we found deficiency. The largest group is that of patients with insufficiency of vitamin D. We didn’t discovered significant difference in the 25(OH)D average values between men and women. There were no significant differences in the average values of the 25(OH)D serum levels when dividing the patients according to their antiretroviral therapy, but after separating the patients by gender, we found that the untreated women had average values of 25(OH)D higher than that of the women treated with EFV. On the next stage of the survey on the 60 HIV-infected patients, who are from the first tested group, we additionally defined the cytokine profile. Our results suggests that increasing 25(OH)D deficiency worsens the damaging of the cellular immune response. The lower levels of vitamin Dare associated with increased levels of IL-6, decreased levels of IL-10, IFN-γ and TNF-α. There’s active immune inflammation when there are reduced 25(OH)D serum levels and it leads to stimulated secretion of the regulatory cytokines and suppression of the Th1 antiviral response. The phase of advanced 25(OH)D deficiency is characterized by parallel depletion of the regulatory and effecter capabilities of CD4 lymphocytes. The recovery of the CD4 lymphocyte pool is difficult because of the lower than average 25(OH)D serum levels, regardless of the conducted antiretroviral therapy.展开更多
文摘AIM: To investigate reactivated Epstein-Barr virus (EBV) infection as a cause for chronic hepatitis. METHODS: Patients with occasionally established elevated serum aminotransferases were studied. HIV, HBV and HCV-infections were excluded as well as any other immunosuppressive factors, metabolic or toxic disorders. EBV viral capsid antigen (VCA) IgG and IgM, EA-R and EA-D IgG and Epstein-Barr nuclear antigen (EBNA) were measured using IFA kits. Immunophenotyping of whole blood was performed by multicolor flow cytometry. CD8+ T cell responses to EBV and PHA were determined according to the intracellular expression of IFN-γ. RESULTS: The mean alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGTP) values exceeded twice the upper normal limit, AST/ALT ratio < 1. Serology tests showed reactivated EBV infection in all patients. Absolute number and percentages of T, B and NK cells were within the reference ranges. Fine subset analysis, in comparison to EBV+ healthy carriers, revealed a significant decrease of naive T cells (P < 0.001), accompanied by increased percentage of CD45RA- (P < 0.0001), and terminally differentiated CD28-CD27- CD8+ T cells (P < 0.01). Moderately elevated numbers of CD38 molecules on CD8+ T cells (P < 0.05) proposed a low viral burden. A significantly increased percentage of CD8+ T cells expressing IFN-γ in response to EBV and PHA stimulation was registered in patients, as compared to controls (P < 0.05). Liver biopsy specimens from 5 patients revealed nonspecific features of low-grade hepatitis.CONCLUSION: Chronic hepatitis might be a manifestation of chronic EBV infection in the lack of detectable immune deficiency; the expansion of CD28- CD27- and increase of functional EBV-specific CD8+ T cells being the only surrogate markers of viral activity.
文摘Today the HIV infection is a chronic disease with significantly longer duration of the life of the patients. Problems of pressing interest are the persistent immune activation and chronic inflammation during the treatment with antiretroviral therapy. Taking this into account, different factors which could affect the immune system and the progress of the HIV infection are being researched. Vitamin D (25(OH)D) is one of those factors if we take note of its effect on the innate and acquired immunity. The aim of this study was to assess 25-hydroxyvitamin D (vitamin D) status in one part of the Bulgarian HIV-infected adult population and to assess connection between 25-hydroxyvitamin D (vitamin D) status and plasma levels of some major cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ). The study includes 145 HIV-positive patients, who are being monitored in the Department for acquired immune deficiency at Specialized Hospital for Infectious and Parasitic Diseases “Proff. Ivan Kirov”—Sofia. From all of the monitored patients only in 15% of the tested we found normal 25(OH)D serum levels, and in 12% of the patients we found deficiency. The largest group is that of patients with insufficiency of vitamin D. We didn’t discovered significant difference in the 25(OH)D average values between men and women. There were no significant differences in the average values of the 25(OH)D serum levels when dividing the patients according to their antiretroviral therapy, but after separating the patients by gender, we found that the untreated women had average values of 25(OH)D higher than that of the women treated with EFV. On the next stage of the survey on the 60 HIV-infected patients, who are from the first tested group, we additionally defined the cytokine profile. Our results suggests that increasing 25(OH)D deficiency worsens the damaging of the cellular immune response. The lower levels of vitamin Dare associated with increased levels of IL-6, decreased levels of IL-10, IFN-γ and TNF-α. There’s active immune inflammation when there are reduced 25(OH)D serum levels and it leads to stimulated secretion of the regulatory cytokines and suppression of the Th1 antiviral response. The phase of advanced 25(OH)D deficiency is characterized by parallel depletion of the regulatory and effecter capabilities of CD4 lymphocytes. The recovery of the CD4 lymphocyte pool is difficult because of the lower than average 25(OH)D serum levels, regardless of the conducted antiretroviral therapy.
