Distinctive immune response patterns of human and murine autoimmune sera to U1 small nuclear ribonucleoprotein C protein

• Published in: The Journal of clinical investigation 1996-06, Vol.97 (11), p.2619-2626
• Main Authors: Satoh, M, Langdon, J J, Hamilton, K J, Richards, H B, Panka, D, Eisenberg, R A, Reeves, W H
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal; Antigen-Antibody Complex; Autoantibodies - blood; Autoantibodies - isolation & purification; Autoimmune Diseases - blood; Autoimmune Diseases - immunology; Cell Line; Humans; Immunoblotting; Immunoglobulin Allotypes; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Ribonucleoprotein, U1 Small Nuclear - immunology; Ribonucleoprotein, U1 Small Nuclear - isolation & purification; Tumor Cells, Cultured
• ISSN: 0021-9738
• DOI: 10.1172/jci118711

The Ul small nuclear ribonucleoprotein (snRNP), a complex of nine proteins with Ul RNA, is a frequent target of autoantibodies in human and murine systemic lupus erythematosus (SLE). Anti-Sm antibodies recognizing the B'/B, D, E, F, and G proteins of Ul snRNPs are highly specific for SLE, and are nearly always accompanied by anti-nRNP antibodies recognizing the Ul snRNP-specific 70K, A, and/or C proteins. Previous studies suggest that human anti-nRNP antibodies recognize primarily the U1-70K and Ul-A proteins, whereas recognition of Ul-C is less frequent. We report here that autoantibodies to U1-C are more common in human autoimmune sera than believed previously. Using a novel immunoprecipitation technique to detect autoantibodies to native Ul-C, 75/78 human sera with anti-nRNP/ Sm antibodies were anti-Ul-C (+). In striking contrast, only 1/65 anti-nRNP/Sm (+) MRL mouse sera of various Igh allotypes was positive. Two of ten anti-nRNP/Sm (+) sera from BALB/c mice with a lupus-like syndrome induced by pristane recognized Ul-C. Thus, lupus in MRL mice was characterized by a markedly lower frequency of anti-U1-C antibodies than seen in human SLE or pristane-induced lupus. The results may indicate different pathways of intermolecular-intrastructural diversification of autoantibody responses to the components of Ul snRNPs in human and murine lupus, possibly mediated by alterations in antigen processing induced by the autoantibodies themselves.