title: A limited lupus anti-spliceosomal response targets a cross-reactive, proline-rich motif.
abstract: 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.
authors.affiliation: Arthritis and Immunology Program, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, 73104, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Arbuckle
authors.forename: A R
authors.initials: AR
authors.lastname: Schilling
authors.forename: J B
authors.initials: JB
authors.lastname: Harley
authors.forename: J A
authors.initials: JA
authors.lastname: James
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000737:chemistry; D003429:Cross Reactions; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D011392:Proline / Q000737:chemistry; D017411:Ribonucleoproteins, Small Nuclear; D017381:Spliceosomes / Q000737:chemistry / Q000276:immunology*; D013997:Time Factors; D055517:snRNP Core Proteins
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D011392:Proline