A LIMITED LUPUS ANTI-SPLICEOSOMAL RESPONSE TARGETS A CROSS-REACTIVE, PROLINE-RICH MOTIF

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease cha racterized by the production of large amounts of characteristic autoan tibodies. Anti-Sm and anti-nRNP (also known as anti-spliceosome) autoa ntibodies are among these. Previous epitope mapping of anti-spliceosom al antibodies has identified multiple antigenic determinants within th is complex immune response. In this report we describe an SLE patient with a relatively simple, long-lasting anti-spliceosomal response. In the earliest serum sample tested the autoimmune response appeared rest ricted to the similar peptides PPPG-MR(P,G)P of Sm B/B', PAPGMRPP of n RNP C, and PPPGMIPP of nRNP A. Unlike all the other tested lupus patie nts with anti-spliceosomal autoantibodies, in this patient these proli ne-rich epitopes remained the primary target for humoral autoimmunity in subsequent serum samples collected over many years, Absorption of a nti-PAPGMRPP antibodies also removed binding to PPPGMR(P,G)P and PPPGM IPP. Isolated antibodies to PAPGMRPP were capable of binding Sm B/B', nRNP C and nRNP A by Western blot. For this particular SLE patient the autoimmune response observed against these three proteins is a single cross-reactive response against a similar proline-rich motif. Also, t his patient has failed to undergo the B cell epitope spreading, typica lly observed in the naturally arising autoimmune response against the spliceosome in human lupus patients. (C) 1998 Academic Press