Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study (original) (raw)
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Clinical Immunology and Immunopathology, 1990
To investigate whether cytomegalovirus (CMV) infection may be related to islet cell antibodies (ICA) production and/or to insulin-dependent diabetes mellitus (IDDM) development, we have analyzed the prevalence of anti-CMV, IgM, and IgG antibodies and of ICA in 80 healthy siblings of IDDM patients (HSIDDP) and in 60 control subjects with negative familiar anamnesis of IDDM. HSIDDP and controls were also typed for HLA-A-B-C and DR antigens. IgM and IgG anti-CMV were detected by an ELISA method, whereas the ICA assay was performed by standard indirect immunofluorescence on 5-p,m unfixed sections of human pancreas. HLA-A-B and C antigens were studied by standard microlymphocytotoxicity; DR antigens were also studied by a standard microlymphocytotoxicity on a B-enriched lymphocyte population. Our results indicate a significant association (P < 0X401) between high titers of anti-CMV IgG antibodies and ICA in HSDIDDP, whereas no correlation was found between the presence of any HLA-A-B-C and DR antigens and the prevalence of anti-CMV IgM and IgG antibodies and/or ICA. Thus, these data may support the hypothesis that a chronic CMV infection may be associated with ICA production whereas other factors seem to be needed for the complete development of type 1 diabetes. Q 1990 Academic press, hc.
Internal Medicine, 2007
We report the case of a 59-year-old woman who developed rapid-onset type 1 diabetes associated with a marked increase in anti-glutamic acid decarboxylase antibody titer (317.5 U/ml), mild increase in HbA1c level (6.8%), diabetic ketoacidosis, and cytomegalovirus enterocolitis. She was a heterozygote for HLA class II DRB1 * 0901-DQA1 * 03-DQB1 * 0303, and she had HLA class I A24, which may have contributed to the rapid beta cell destruction. Based on the putative molecular mimicry of GAD65 by cytomegalovirus antigen, we hypothesize that the type 1 diabetes in this case was associated with cytomegalovirus infection.
Transplant International, 2010
Association of type 1 diabetes and cytomegalovirus (CMV) is suspected and CMV infections have also been linked to increased risk of new onset posttransplantation diabetes. We monitored response to islet autoantigens, pancreatic endocrine function, and CMV infections in one type 1 diabetic patient receiving pancreas allograft. Time course analyses of levels of islet autoantibodies (Abs), IFN-c ELISPOT response, analysis of T cell function, levels of C peptide together with CMV pp65 antigenaemia and viraemia and graft biopsy histopathology were performed in comparison with a cohort of diabetic recipients. Evidence of autoimmune activation to GAD and IA2, modification of CD4 + CD25hi T cells, loss of pancreatic function, concomitantly with multiple CMV infections and allograft rejection with peri-insulitis is provided. The parallel between metabolic outcome, initiation and progression of autoreactivity to islet autoantigens and early CMV infections after transplantation, suggests that persistent CMV infections may be relevant to the pathogenesis of type 1 diabetes.
Cytomegalovirus (CMV) and Coxsackievirus (CV) are included in the environmental factors potentially relevant to the pathogenesis of type 1 diabetes (T1D). Thus, this study aimed to detect the prevalence of both anti-IgG for each of CV and CMV in diabetic children with (EV +) or without (EV-) enteroviruses infection. The current study revealed that the T1D-EV + and T1D-EV-groups had marked elevations in hemoglobin A1c (HbA1c), C-reactive protein (CRP) and glutamic acid decarboxylase autoantibodies (GADA) as compared to non-diabetic control. Moreover, anti-IgG for the CV and CMV groups were detected in three groups; diabetic infected (T1D-EV +), diabetic non-infected (T1D-EV-) and control group. Detection of anti-CV IgG achieved 22.7%, 6.7% and 64% in control, T1D-EV-and T1D-EV + , respectively. However, detection of anti-CMV IgG revealed 23.4%, 50% and 40% in control, T1D-EV-and T1D-EV + , respectively. In conclusion, the prevalence of the antibodies of CV-IgG and CMV-IgG in the sera of diabetic children more than that in healthy control children may give a role of these viruses in the etiology and progression of T1D.
Early childhood CMV infection may decelerate the progression to clinical type 1 diabetes
Pediatric Diabetes, 2018
Aims/Hypothesis Evidence of the role of cytomegalovirus (CMV) infection in the pathogenesis of type 1 diabetes (T1D) has remained inconclusive. Our aim was to elucidate the possible role of CMV infection in the initiation of islet autoimmunity and in the progression to clinical T1D among children with HLA-conferred T1D risk. Methods A total of 1402 children from the prospective Type 1 Diabetes Prediction and Prevention (DIPP) study were analyzed for CMV-specific IgG antibodies during early childhood. All children carried HLA-DQ genotypes associated with increased risk for T1D. The effect of CMV infection on the appearance of T1D-associated autoantibodies (IAA, GADA and IA-2A, n=356) and on the progression rate to clinical T1D (n=233) were analyzed with Kaplan-Meier survival analysis and logrank test.
Prospective study of cytomegalovirus seropositivity and risk of mortality from diabetes
Acta Diabetologica, 2014
Cytomegalovirus (CMV) infects 40 % of the world population and has been suggested to be associated with diabetes; however, no prospective study has ever examined diabetes mortality associated with the infection. A cohort of 14,404 non-diabetic adult participants aged 17-90 years from the Third National Health and Nutrition Examination Survey (1988-1994) was prospectively followed for mortality through 2006. CMV immunoglobulin G was measured by enzyme-linked immunosorbent assay and immunofluorescence assay. Diabetes death was assessed with death records from the National Death Index. Cox proportional hazards modeling was used to determine diabetes mortality risk associated with CMV infection, adjusting for socio-demographics, diabetes risk factors, and comorbidities. At baseline, 76.8 % of subjects were CMV seropositive, and after an average follow-up of 13.7 years, diabetes mortality rate per 10,000 person-years was 6.8 (95 % CI 5.7, 8.0). Among seropositive participants, the diabetes death rate (8.4, 95 % CI 7.0, 9.9) was more than four times the rate in seronegative ones (2.0, 95 % CI 1.1, 3.6) (P value for the difference \0.001). In the adjusted Cox proportional hazards analysis, CMV seropositivity more than doubled the risk of diabetes mortality (HR 2.06, 95 % CI 1.05, 4.06). CMV infection may thus predict future mortality from diabetes in non-diabetic people.