Anti-ribosomal P protein antibody in human systemic lupus erythematosus up-regulates the expression of proinflammatory cytokines by human peripheral blood monocytes

Autor: Shunsei Hirohata, Yoshiyuki Arinuma, Tatsuo Nagai, Kazuhiko Yamamoto, Tamiko Yanagida
Rok vydání: 2005
Předmět:
Zdroj: Arthritis & Rheumatism. 52:847-855
ISSN: 1529-0131
0004-3591
DOI: 10.1002/art.20869
Popis: Objective Autoantibodies to ribosomal P proteins (anti-P antibodies) are detected in 12–16% of patients with systemic lupus erythematosus (SLE) and have been found to be associated with some manifestations of the disease, including lupus psychosis and hepatitis. Recent studies have disclosed that anti-P antibodies react with activated T cells but not with B cells, suggesting possible direct effects of anti-P antibodies on immune regulation. The present study was designed to explore the presence of the epitope recognized by anti-P antibodies on human peripheral blood monocytes. Methods Highly purified peripheral blood monocytes obtained from healthy donors were cultured with or without interferon-γ (IFNγ) in the presence of either anti-P antibodies purified by affinity chromatography from the sera of patients with SLE or control IgG. Results Flow cytometry analysis disclosed that fresh (day 0) monocytes did not express the ribosomal P epitope, whereas expression of the ribosomal P epitope was induced on annexin V–negative monocytes after activation through plastic adherence for 48 hours. More important, anti-P antibodies (compared with normal IgG or IgG from SLE patients devoid of anti-P antibodies) enhanced the production of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) by activated monocytes. Accordingly, anti-P antibodies also up-regulated the expression of TNFα and IL-6 messenger RNA in activated monocytes. Of note, F(ab′)2 fragments of anti-P antibodies, which do not result in Fcγ receptor (FcγR) crosslinking, also effectively up-regulated the expression of TNFα and IL-6. Conclusion These results indicate that human peripheral blood monocytes express the ribosomal P epitope upon activation, irrespective of induction of apoptosis. Moreover, the data suggest that anti-P antibodies might modify a variety of inflammatory responses through up-regulation of the expression of proinflammatory cytokines in monocytes, in a manner that does not involve FcγR crosslinking.
Databáze: OpenAIRE
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