Aims/hypothesis Type 1 diabetes is an autoimmune disease resulting from a complex interplay between genetic and environmental factors. Cytomegalovirus (CMV) infection is one of the environmental factors implicated in the development of type 1 diabetes, although the association remains unproven. We aimed to clarify the possible correlation between CMV infections and type 1 diabetes-associated autoimmunity at the time point of autoantibody appearance in young children with HLA-conferred disease susceptibility.Methods CMV-specific IgG antibodies were analysed from serum samples of 169 children who had developed the first type 1 diabetes-associated autoantibody by the age of 2 years and who turned positive for multiple autoantibodies during later follow-up. We also studied 791 control children matched for sex, age and HLA genotype. The subsequent progression to clinical diabetes was analysed. The serum specimens used were collected at the time of autoantibody seroconversion or within the next 6 months. Results The frequency of CMVantibodies was similar in both study groups at the time of the first autoantibody appearance. Of the index children, 38 (22.5%) were CMV IgG antibodypositive, while the figure for control children was 206 (26.0%; p=0.38). No association between perinatal CMV infection and progression to type 1 diabetes was observed. Conclusions/interpretation According to these results, perinatal CMV infections are not associated with early serological signs of beta cell autoimmunity or progression to type 1 diabetes in children with diabetes risk-associated HLA genotype.
To clarify when antibodies against cytomegalovirus (CMV), varicella-zoster virus (VZV) and herpes simplex virus (HSV) develop among young children, 1206 serum samples collected prospectively from 199 children born in 1989 and 1990 were studied. The samples were drawn at the ages of 7 and 13 months, then yearly until the age of 5 y and then at 7 and 8 y. In each age group at least 106 samples were collected. Immunoglobulin G class antibodies to the 3 viruses were measured using an enzyme immunoassay. At the age of 7 months 27% of the children had CMV antibodies, whereas only 3% had antibodies against VZV and 2% against HSV. The prevalence of seropositivity for CMV increased slowly to 41% by the age of 8 y. Seroconversions to VZV antibody positivity occurred frequently after 2 y of age, so that by 8 y 83% of children had VZV antibodies. The proportion of children with HSV antibodies remained low throughout the study, as only 17% of children had HSV antibodies at the age of 8 y. The data show that HSV infection is becoming acquired later in life and the proportion of uninfected children is increasing. The proportion of CMV infections during the perinatal period and early infancy remains high, in one-third of the children, and most children also have VZV infection during the early years of life.
Objective-Chronic Chlamydia pneumoniae (Cpn), Helicobacter pylori (Hp), and herpes virus infections have been associated with atherogenic serum lipid profile and an excess of cardiovascular events in adults. Because mechanisms leading to atherosclerosis are active since early childhood, we examined whether Cpn, Hp, or cytomegalovirus (CMV) seropositivity relates to serum lipid, lipoprotein, or apolipoprotein concentrations in children. We also looked for factors increasing probability of Cpn seropositivity in children. Methods and Results-Cpn-specific IgG and IgA, as well as Hp-specific and CMV-specific IgG antibodies were assessed by enzyme immunoassay in 199 apparently healthy children, followed-up from 7 to 11 years of age. Serum lipid profiles were studied at the ages of 7, 9, and 11 years using standard methods. (Cpn), an intracellular Gram-negative bacterium commonly causing respiratory tract infections. Coronary artery disease (CAD) and Cpn infections share predisposing factors, such as old age and smoking, that increase the risk of CAD and chronic Cpn infection, 6 known to associate with ischemic heart disease and acute myocardial infarction. 7,8 A prominent hypothesis has been that the increased CAD risk in connection with a chronic Cpn infection might be mediated by the induction of a proatherogenic lipoprotein profile as the acute phase response to an infection, targeted primarily to protect the host from further injury, is accompanied by changes in the lipid metabolism similar to those proposed to promote atherogenesis. These changes comprise, in particular, raised concentration of triglycerides 9 and decreased concentration of high-density lipoprotein (HDL) cholesterol. 10 In fact, lipid profiles in adults with persisting Cpn seropositivity without respiratory tract symptoms resembled those seen during acute infections. 11 Interestingly, Helicobacter pylori (Hp), another Gram-negative bacterium causing chronic infection of the gastric mucosa, and cytomegalovirus (CMV), a herpes virus, in adults have been associated with CAD, 12,13 as well as with disturbances in lipid and lipoprotein metabolism. 14 -16 These observations further suggest that alteration of lipid metabolism by chronic bacterial and viral infections might contribute to the development of atherosclerosis.We recently demonstrated that a sizeable proportion of 7-to 8-year-old children have persistently elevated Cpn IgG and IgA antibody values, 17 supporting the contention that chronic Cpn infections might exist already in early childhood. In this study, we examined whether Cpn, Hp, or CMV seropositivity is associated with proatherogenic serum lipid values in prospectively followed-up 7-to 11-year-old healthy children, as has been documented in adults. Because of some contradictory findings in studies addressing the relationship between Cpn seropositivity and socioeconomic and lifestyle Methods Study Design and SubjectsThe design and protocol of the ongoing STRIP study (Special Turku Coronary Risk Factor Intervention Project for Childr...
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