{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T15:21:07Z","timestamp":1765380067672},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T00:00:00Z","timestamp":1235606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The U1 small nuclear RNPs are common targets of autoantibodies in lupus and other autoimmune diseases. However, the etiology and progression of autoimmune responses directed against these antigens are not well understood. The aim of this study was to use a unique collection of serial samples obtained from patients before and after the development of nuclear RNP (nRNP) antibodies to investigate early humoral events in the development of anti\u2010nRNP autoimmunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lupus patients with sera available from both before and after the development of nRNP antibody precipitin were identified from the Oklahoma Clinical Immunology Serum Repository. Antibodies in the serial samples were analyzed by enzyme\u2010linked immunosorbent assay, Western blotting, solid\u2010phase epitope mapping, and competition assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The first\u2010detected nRNP antibodies targeted 6 common initial epitopes in nRNP A, 2 in nRNP C, and 9 in nRNP 70K. The initial epitopes of nRNP A and nRNP C were significantly enriched for proline and shared up to 95% sequence homology. The initial nRNP 70K humoral epitopes differed from those of nRNP A and nRNP C. The initial antibodies to nRNP A and nRNP C were cross\u2010reactive with the SmB\u2032\u2010derived peptide PPPGMRPP. Antibody binding against all 3 nRNP subunits diversified significantly over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Autoantibodies to nRNP A and nRNP C initially targeted restricted, proline\u2010rich motifs. Antibody binding subsequently spread to other epitopes. The similarity and cross\u2010reactivity between the initial targets of nRNP and Sm autoantibodies identifies a likely commonality in cause and a focal point for intermolecular epitope spreading.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24306","type":"journal-article","created":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T13:15:27Z","timestamp":1235654127000},"page":"848-859","source":"Crossref","is-referenced-by-count":32,"title":["Early targets of nuclear RNP humoral autoimmunity in human systemic lupus erythematosus"],"prefix":"10.1002","volume":"60","author":[{"given":"Brian D.","family":"Poole","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca I.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel M.","family":"Guthridge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathy 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