A PROSPECTIVE-STUDY OF THE ROLE OF COXSACKIE-B AND OTHER ENTEROVIRUS INFECTIONS IN THE PATHOGENESIS OF IDDM

Coxsackievirus B infections have been associated with clinical manifes tation of insulin-dependent diabetes mellitus (IDDM) in several studie s, but their initiating role in the slowly progressing beta-cell damag e is not known. This is the first prospective study designed to assess the role of coxsackie B and other enterovirus infections in the induc tion and acceleration of this process, Three separate series were stud ied: 1) an intrauterine exposure series comprising 96 pregnant mothers whose children subsequently manifested IDDM and 96 control mothers wh ose children remained nondiabetic; 2) a cohort of 22 initially unaffec ted siblings of diabetic children who were followed until they develop ed clinical IDDM (mean observation time, 29 months) and 110 control si blings who remained nondiabetic; 3) a case-control series comprising 9 0 children with newly diagnosed IDDM and 90 control subjects, Enterovi rus infections were identified on the basis of significant increases i n serum IgG, IgM, or IgA class antibodies against a panel of enterovir us antigens (capture radioimmunoassay). Enterovirus antibodies were si gnificantly elevated in pregnant mothers whose children subsequently m anifested IDDM, particularly in cases in which IDDM appeared at a very young age, before the age of 3 years (P < 0.005), Serologically verif ied enterovirus infections were almost two times more frequent in sibl ings who developed clinical IDDM than in siblings who remained nondiab etic (mean, 1.0 vs, 0.6 infections/follow-up year; P < 0.001), This di fference was seen both close to the diagnosis of IDDM and several year s before diagnosis, Up to 19% (10 of 52) of the infections in prediabe tic siblings were associated with increases in islet cell antibody (IC A) levels, and 83% (10 of 12) of ICAs increase with enterovirus infect ions, The corresponding figures in control siblings were 3% (5 of 185, P < 0.001) and 38% (5 of 13, NS), IgM class enterovirus antibodies we re slightly elevated in young children (< 3 years old) with newly diag nosed IDDM (P < 0.05), but not in older patients, These observations s uggest that exposures to enterovirus infections, both in utero and in childhood, are able to induce beta-cell damage and lead to clinical ID DM after a varying subclinical period.