Indications that maternal coxsackie B virus infection during pregnancy is a risk factor for childhood-onset IDDM

Abstract

In a population-based setting, we traced serum samples collected at time of birth from 55 mothers whose children later developed insulin-dependent diabetes (IDDM) and matched them pairwise to control subjects who gave birth at the same hospital during the same month. The sera were analysed for IgM antibodies to coxsackie B virus serotypes 2, 3 and 4 (CBV-2, 3 and 4) using a type-specific mu-antibody-capture radioimmunoassay. Despite a decreased power due to the close matching by time of birth we found a significantly higher frequency of CBV-3 IgM at delivery in mothers whose children later became diabetic compared to their matched control subjects. When using the presence of CBV-3 IgM as a risk factor the Mantel-Haenszel odds ratio estimate (95% confidence limits) was 2.57 (1.02; 7.31), p = 0.043. For CBV-2 and CBV-4, respectively no significant difference was found between mothers of patients and control subjects. According to the odds ratio estimate for CBV-3 and the proportion of exposed mothers among patients estimated in this study the aetiological fraction for this risk determinant would be 27%. In conclusion, this study indicates that children of mothers who expressed CBV IgM at delivery are at increased risk for developing childhood onset IDDM. A fetal infection with CBV similar to rubella virus may initiate autoimmunity or cause persistent infection that may lead to progressive beta-cell destruction.

Diabetes-associated HLA genotypes affect birthweight in the general population

“…Numerous triggers for type 1 diabetes have been proposed. These include viral infections [39][40][41], dietary factors (cow's milk, nitrosamines, high protein intake) [42,43], neonatal jaundice and ABO incompatibility [44], neonatal respiratory disease [44], early supplementary milk-based feeding, short time of breast-feeding [42,45] and stress events such as severe life events [42,46,47]. Several studies have found that children who later develop diabetes have a higher BW than controls, and also have an increased linear growth in childhood [15,16,42,48,49].…”

Coxsackievirus B4 infection of murine foetal thymus organ cultures

“…Vertical transmission of CV-B associated with foetal thymus infection has been reported [Iwasaki et al, 1985;Lozovskaia et al, 1997]. In addition, it has been shown that enterovirus infections in utero may induce b-cell autoimmunity [Otonkoski et al, 2000], and that CV-B4 infection during pregnancy was a risk factor for childhood-onset type 1 diabetes [Dahlquist et al, 1995;Hyöty et al, 1995].…”

“…It has been suggested that foetal infection with CV-B may initiate autoimmunity or cause persistent infection that may lead to a progressive b-cell destruction and thus could play a role in the pathogenesis of type 1 diabetes [Dahlquist et al, 1995]. Furthermore, massive thymic depletion and/or CV-B4 E2-induced abnormal lymphocyte maturation have been linked to autoimmunity with possible insulitis and hyperglycaemia in mice models [Chatterjee et al, 1992;Shih et al, 2004].…”

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

“…The HLA-DQ locus on chromosome 6p21 confers the strongest genetic risk for T1D (24). The majority of individuals with these genetic risk factors do not develop T1D and several environmental factors have been considered including infections (6,13,34,40), climate (35), diet (3,21), and stress (16). The possible influence of viral infections as a trigger of islet autoimmunity or clinical onset of T1D has been reported in numerous studies (5,19).…”