Correlation between islet cell antibodies and anti-cytomegalovirus IgM and IgG antibodies in healthy first-degree relatives of type 1 (insulin-dependent) diabetic patients

Nicoletti, Ferdinando; Scalia, Guido; Lunetta, M; Condorelli, Francesca; Mauro, Maria Gaetana Di; Barcellini, Wilma; Stracuzzi, S.; Pagano, Maria Carmen; Meroni, Pier Luigi

doi:10.1016/0090-1229(90)90075-2

Cited by 29 publications

(21 citation statements)

References 20 publications

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“…It has been suggested that CMV infections may play a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) by inducing or promoting the autoimmune process against beta cells. This has been supported by observations that the presence of the CMV genome and islet cell antibodies (ICA) are correlated in patients with newly-diagnosed IDDM [2], and that high titres of IgG class antibody against CMV are associated with ICA in healthy siblings of diabetic children [3]. Furthermore, immunological cross-reactivity between CMV and an islet cell 38 kDa autoantigen has been described [4].…”

Section: Discussionsupporting

confidence: 52%

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Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study

et al. 1995

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SummaryTo study the possible temporal association between primary cytomegalovirus infection and the appearance of islet cell autoantibodies or the development of insulin-dependent diabetes mellitus (IDDM) cytomegalovirus antibodies were analysed from follow-up sera of 46 initially non-diabetic siblings of diabetic children who either manifested clinical IDDM (22 siblings) or turned islet cell antibody positive (24 siblings) during the prospective observation (mean follow-up time 2.9 years). Secondly, cytomegalovirus antibodies were analysed during pregnancy in 96 mothers whose child presented with IDDM before the age of 7 years and in 96 control mothers who gave birth to a non-diabetic child. Thirdly, a case-control series including 90 newly-diagnosed young children with IDDM and their 90 control subjects was analysed. No seroconversions were found in cytomegalovirus antibodies during the follow-up of the 46 siblings indicating no temporal association with islet cell antibody seroconversion or manifestation of clinical diabetes. During the followup 17 (37 %) siblings were constantly seronegative and 29 (63 %) seropositive for cytomegalovirus IgG and there was no difference between islet cell antibody positive and negative siblings. Cytomegalovirus IgG and IgM were not different in pregnant mothers who gave birth to a subsequently diabetic child compared to control mothers, or in newly-diagnosed diabetic children compared to control children. Cytomegalovirus IgA was higher in newly-diagnosed diabetic children than in control children (p < 0.005). This difference disappeared when only cytomegalovirus IgG positive individuals were analysed. No correlation was found between islet cell antibodies and cytomegalovirus antibodies in newly-diagnosed diabetic patients. The results do not support the hypothesis that primary cytomegalovirus infections could initiate the cascade leading to autoimmune destruction of the beta cells. [Diabetologia (1995) 38: 705-710]

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Section: Discussionsupporting

confidence: 52%

“…The role of CMV in the pathogenesis of IDDM has been proposed in some earlier reports [2][3][4][5]13]. However, such a connection has not been found in all studies, for example in two separate reports there was no evidence of recent CMV infection in patients with newly-diagnosed IDDM [14,15].…”

Section: Discussionmentioning

confidence: 71%

Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study

et al. 1995

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“…Furthermore, 80% of patients who had both anti-CMV antibodies and the CMV genome also had islet cell autoantibodies [34]. Another study found that nondiabetic siblings of T1D patients had a significant association between high titres of anti-CMV antibodies and islet cell autoantibodies, but no correlation between anti-CMV antibodies with HLA-DR antigens [109]. These results suggest that chronic CMV infection may be associated with islet cell autoantibody production, but that other factors may be needed for the development of clinical T1D.…”

Section: Cytomegalovirusmentioning

confidence: 95%

A New Look at Viruses in Type 1 Diabetes

Jun¹,

Yoon²

2004

ILAR Journal

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Type 1 diabetes results from the destruction of pancreatic beta cells. Genetic factors are believed to be a major component for the development of type 1diabetes, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that non-genetic factors play an important role in the expression of the disease. Viruses are one environmental factor that is implicated in the pathogenesis of type 1 diabetes. To date, 14 different viruses have been reported to be associated with the development of type 1 diabetes in humans and animal models. Viruses may be involved in the pathogenesis of type 1 diabetes in at least two distinct ways: by inducing beta cellspecific autoimmunity, with or without infection of the beta cells, (e.g. Kilham rat virus) and by cytolytic infection and destruction of the beta cells (e.g. encephalomyocarditis virus in mice). With respect to virus-mediated autoimmunity, retrovirus, reovirus, Kilham rat virus, bovine viral diarrhoea-mucosal disease virus, mumps virus, rubella virus, cytomegalovirus and Epstein-Barr virus are discussed. With respect to the destruction of beta cells by cytolytic infection, encephalomyocarditis virus, mengovirus and Coxsackie B viruses are discussed. In addition, a review of transgenic animal models for virus-induced autoimmune diabetes is included, particularly with regard to lymphocytic choriomeningitis virus, influenza viral proteins and the EpsteinBarr viral receptor. Finally, the prevention of autoimmune diabetes by infection of viruses such as lymphocytic choriomeningitis virus is discussed.

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“…Single‐case reports of IDDM after cytomegalovirus (CMV) infection have been reported in children68 and adults 69‐71. More indirect evidence came from studies showing that 35% of newly diagnosed IDDM patients showed serological evidence of recent CMV infection and association with islet cell autoantibodies 70,72‐74. On the other hand a prospective study from Sweden screening 16,474 newborns for congenital CMV infection was unable to detect any correlation of CMV infection with diabetes 75.…”

Section: Cytomegalovirusmentioning

confidence: 99%

Viruses and Diabetes

Jaeckel

Manns

Herrath

2002

Annals of the New York Academy of Sciences

112

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Insulin‐dependent diabetes mellitus (IDDM) is a multifactorial disease. Besides a genetic predisposition environmental factors have been implicated in the pathogenesis of β cell destruction. Among these environmental factors viruses have been the focus of many studies. Some viruses are diabetogenic in animals, and others have been implicated as triggers in human IDDM by temporal and geographical association between IDDM and viral infections, serological evidence of infection in recently diagnosed diabetic patients, and the isolation of viruses from the pancreas of affected individuals. We discuss possible pathomechanisms of viral infections in β cell destruction and review the studies on involvement of enteroviruses, retroviruses, rubella viruses, cytomegaloviruses, and Epstein‐Barr viruses in human IDDM. We also report on studies of diabetogenic viruses in animal models as well as on viral infections protecting from IDDM. Some of the difficulties in linking viral infections to IDDM will be illustrated with data from a transgenic mouse model in which IDDM can be precipitated by infections with certain strains of lymphocytic choriomeningitis virus (LCMV). Emerging treatment concepts that do not rely on defining the initiating autoantigens but involve self‐reactive regulatory lymphocytes such as oral antigen administration, as well as DNA vaccines, will be discussed briefly.

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Correlation between islet cell antibodies and anti-cytomegalovirus IgM and IgG antibodies in healthy first-degree relatives of type 1 (insulin-dependent) diabetic patients

Cited by 29 publications

References 20 publications

Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study

Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study

A New Look at Viruses in Type 1 Diabetes

Viruses and Diabetes

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