A Limited Lupus Anti-Spliceosomal Response Targets a Cross-Reactive, Proline-Rich Motif

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of large amounts of characteristic autoantibodies. Anti-Sm and anti-nRNP (also known as anti-spliceosome) autoantibodies are among these. Previous epitope mapping of anti-spliceosomal antibodies has identified multiple antigenic determinants within this 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 restricted to the similar peptides PPPGMR(P,G)P of Sm B/B′, PAPGMRPP of nRNP C, and PPPGMIPP of nRNP A. Unlike all the other tested lupus patients with anti-spliceosomal autoantibodies, in this patient these proline-rich epitopes remained the primary target for humoral autoimmunity in subsequent serum samples collected over many years. Absorption of anti-PAPGMRPP antibodies also removed binding to PPPGMR(P,G)P and PPPGMIPP. 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, this patient has failed to undergo the B cell epitope spreading, typically observed in the naturally arising autoimmune response against the spliceosome in human lupus patients.