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Viruses and their roles in immune mediated disease: another piece to this complex puzzle.

Has medical research reached the stage where advances in immunology and genetics could explain what causes the immune system to respond at a certain time by damaging normal tissues instead of eliminating an invading microbe? Despite medical and technological progress, the major clinical problems of autoimmunity remain unsolved (1). In this issue of the Journal, Carlsson et al. report on their search for enterovirus infection during pregnancy and supply the scientific community with additional data for possible viral triggering in immune-mediated diseases. She and her colleagues found no conclusive evidence in this Swedish cohort that enterovirus infection during pregnancy is a triggering factor in the fetus to develop celiac disease in childhood. Considering the broad spectrum of autoimmune diseases and the host of infectious agents which have been accused of giving rise to the development or progression of immune mediated pathologic responses, it seems logical that the search for the single, initiating microbe or virus will continue for a longer time. Should a monocausal infectious trigger even exist for a defined autoimmune process, many articles presenting negative epidemiologic data will still need to be published over the coming years. This data should help us to encircle major candidates in the microbial world. Advances in modern genetics have contributed to our understanding of susceptibility to autoimmune diseases. The major histocompatibility complex HLA region on chromosome 6p21 contains the major locus of type 1 diabetes, common allelic variants at the class II HLADRB1, -DQA1, and -DQB1 loci account for the majority of IDDM1 (2). The same regions—and CTLA4 gene— are of importance in Graves’ disease (3). Carlsson et al. also refer to associated susceptibility on HLA-DQA1 and –DQB1 for celiac disease (4). Nevertheless, a population-based study indicates that the concordance rate for the development of IDDM between monocygotic twins (5) as well as for Graves’ hyperthyroidism is only about 35% (6). Therefore, genetic factors are certainly necessary but are not sufficient alone for the development of autoimmune diseases. The concept of environmental factors triggering the immune-mediated process seems logical. Besides stressful life events and hormonal factors, the role of infectious agents is of great investigative interest. Most data available reflects on IDDM. Enterovirus, especially Coxsackie virus B, became an early candidate for infectious triggering of islet cell destruction based on serological and epidemiologic studies focused on IgM responses in children who developed IDDM (7,8). Later the use of reverse transcriptase polymerase chain reaction to detect enterovirus RNA suggested that CVB infection may be associated with clinical IDDM (9) and that enterovirus RNA in serum is a risk factor for betacell autoimmunity in prediabetic children (10). The PCR technique has significantly enhanced the sensitivity of detecting viral genomes in serum and tissue samples—an even greater amount of epidemiologic data is to be expected through growing use of this method. The prevalence of associated autoimmune disorders, like multiorgan-specific autoimmune endocrinopathy, is also thought to be provoking (11). The question arises that if enterovirus plays a part in IDDM development, could this also be the case in other autoimmune diseases? Received February 27, 2002; accepted March 4, 2002. Address correspondence to Robert Pichler, MD, PhD, Institute of Nuclear Medicine and Endocrinology, AKH Linz, Krankenhausstr. 9, A-4020 Linz, Austria (e-mail: Robert.Pichler@akh.linz.at). This editorial accompanies an article. Please see Enterovirus Infection During Pregnancy is Not a Risk Factor for Celiac Disease in the Offspring. A.K. Carlsson, B.A. Lindberg, A.C.A. Bredberg, H. Hyöty, S.-A. Ivarsson. J Pediatr Gastroenterol Nutr 2002;35:649–652. Journal of Pediatric Gastroenterology and Nutrition 35:597–599 © November 2002 Lippincott Williams & Wilkins, Inc., Philadelphia