Abstract
Clinicians who care for patients with various connective tissue diseases frequently employ measurements of autoantibodies such as rheumatoid factors (RFs), anti-Sm antibodies, or anti-neutrophil cytoplasmic antibodies (cANCA) as a method to follow patients. Although the primary specificity of RFs appears to be directed against the Fc portion (C gamma 3 and C gamma 2 domains) of IgG, epitope mapping studies have now also demonstrated that many RFs also react with linear regions on beta 2-microglobulin and Class I HLA molecules. Cross reacting regions of IgG, beta 2m, and HLA Class I frequently show immunodominant tyrosines, trytophanes, valines, leucines, glutamic acids, aspartic acids, and threonines. Immunodominant linear epitopes on Sm antigen may be limited to regions expressing the PPPGMRPP or PPPGIRGP motifs. A number of linear regions of Proteinase 3 reacting with IgG antibodies in the sera of patients with Wegener's granulomatosis have now been identified. However, affinity purified rabbit antibodies to two of these major PR3 antigenic sties (ATVQLPQ and RVGAHDP) linked to Sepharose to form affinity columns, absorbed equal amounts of a mixture of many serum proteins from both Wegener's patients and normal controls. Continued study of this interface between autoantibody production, disease, and normal immune modulation is necessary.
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