Cluster analysis of human autoantibody reactivities in health and in type 1 diabetes mellitus: a bio-informatic approach to immune complexity

Informatic methodologies are being applied successfully to analyze the complexity of the genome. But beyond the genome, the immune system reflects the state of the body in health and disease. Traditionally, immunologists have reduced the immune system, where possible, to one-to-one relationships between particular antigens and particular antibodies or T-cell clones. Autoimmune diseases, caused by an immune attack against a body component, are usually investigated by following the response to single self-antigens. In this study, we apply informatics to analyze patterns of autoantibodies rather than single species of autoantibodies. This study was designed not to replace traditional approaches to immune diagnosis, but to test whether meaningful patterns of autoantibodies might exist. Using an unbiased solid-phase ELISA antibody test, we detected serum IgG and IgM antibodies in the sera of 20 healthy persons and 20 persons with type I diabetes mellitus binding to an array of 87 different antigens, mostly self-antigens. The healthy subjects manifested autoantibodies to a variety of self-antigens, many known to be associated with autoimmume diseases. We investigated the patterns of these autoantibodies using a coupled two-way clustering algorithm developed for analyzing data from gene arrays. We now report that the reactivity patterns of autoantibodies to particular subsets of self-antigens exhibited non-trivial structure, which significantly discriminated between healthy persons and persons with type I diabetes. The results show that despite the wide prevalence of autoantibodies, the patterns of reactivity to defined subsets of self-antigens can provide information about the state of the body. (C) 2003 Elsevier Ltd. All rights reserved.