Journal of Autoimmunity (1988) zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG 1,499-506 - The Role of Antigen in Autoimmune Responses with Special Reference to Changes in Carbohydrate Structure of IgG in Rheumatoid Arthritis Ivan M. Roitt,*t Raymond A. Dwek,$ Rajesh B. Parekh,$ Thomas W. Rademacher,$ Azita Alavi,* John S. Axford,? Katherine B. Bodman,* Angela Bond,* Anne Cooke,* Frank C. Hay,*? David A. Isenberg,l_ Peter M. Lydyard,*l_ Lorna Mackenzie,* Graham Rook& Mark Smith* and Nazira Sumarf Departments of *Immunology, tRheumatology Research, and § M icrobiology , University College zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA and M iddlesex School of M edicine, zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR London W l; $Glycobiology Unit, Department of Biochemistry, University of Oxford, Oxford, UK Evidence indicating an important role for antigen in the provocation of autoimmune responses is presented. Attention is especially focused on carbohydrate abnormalities in IgG in rheumatoid arthritis, since auto- sensitization to this molecule is thought to be of central importance in the pathogenesis of this disease. A higher percentage of Fey oligosaccharide chains in the serum IgG of patients with rheumatoid arthritis lack terminal galactose residues rela- tive to age-matched controls. This does not appear to be a characteristic feature of chronic inflammatory diseases in general. A new, more rapid assay for agalactosyl chains is described and shown to give results compar- able to the more conventional biochemical analysis. The defect probably arises from a reduction in activity of B-cell galactosyltransferases. The galactose changes may contribute to the autoantigenicity of IgG and could facilitate the self-association of IgG rheumatoid factors. - Introduction For many years, studies on the mechanisms underlying the development of auto- immune diseases were directed largely at the identification of abnormalities in the immune response. Recently, however, there has been a greater awareness of the possible role played by antigen and its presentation (see for example Roitt, [l]). zyxwvutsrqpo Correspondence to: Professor I. M. Roitt, Department of Immunology, University College and Middlesex School of Medicine, Arthur Stanley House, 40-50 Tottenham Street, London Wl P 9PG, UK. 499 0896-841 l/88/060499+08 $03.00/O 0 1988 Academic Press Limited