Open AccessAnti–ribosomal P protein antibody in human systemic lupus erythematosus up‐regulates the expression of proinflammatory cytokines by human peripheral blood monocytes
Author(s) -
Nagai Tatsuo,
Arinuma Yoshiyuki,
Yanagida Tamiko,
Yamamoto Kazuhiko,
Hirohata Shunsei
Publication year - 2005
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.20869
Subject(s) - antibody , immunology , autoantibody , proinflammatory cytokine , epitope , lupus erythematosus , tumor necrosis factor alpha , immune system , monocyte , systemic lupus erythematosus , medicine , microbiology and biotechnology , biology , inflammation , disease
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.