IMMUNITY IN THE CONNECTIVE-TISSUE DISEASES - THE HUMORAL SIDE OF THE COIN

Clinicians who care for patients with various connective tissue diseas es frequently employ measurements of autoantibodies such as rheumatoid factors (RFs), anti-Sm antibodies, or anti-neutrophil cytoplasmic ant ibodies (cANCA) as a method to follow patients. Although the primary s pecificity of RFs appears to be directed against the Fc portion (C(gam ma)3 and C(gamma)2 domains) of IgG, epitope mapping studies have now a lso demonstrated that many RFs also react with linear regions on beta( 2)-microglobulin and Class I HLA molecules. Cross reacting regions of IgG, beta(2)m, and HLA Class I frequently show immunodominant tyrosine s, trytophanes, valines, leucines, glutamic acids, aspartic acids, and threonines. Immunodominant linear epitopes on Sm antigen may be limit ed to regions expressing the PPPGMRPP or PPPGIRGP motifs. A number of linear regions of Proteinase 3 reacting with IgG antibodies in the ser a 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 aff inity columns, absorbed equal amounts of a mixture of many serum prote ins from both Wegener's patients and normal controls. Continued study of this interface between autoantibody production, disease, and normal immune modulation is necessary.