Anti-ribosomal P protein antibody in human systemic lupus erythematosus up-regulates the expression of proinflammatory cytokines by human peripheral blood monocytes.
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-gamma (IFNgamma) 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 alpha (TNFalpha) and interleukin-6 (IL-6) by activated monocytes. Accordingly, anti-P antibodies also up-regulated the expression of TNFalpha and IL-6 messenger RNA in activated monocytes. Of note, F(ab')(2) fragments of anti-P antibodies, which do not result in Fcgamma receptor (FcgammaR) crosslinking, also effectively up-regulated the expression of TNFalpha and IL-6.


CONCLUSIONS
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 FcgammaR crosslinking.
Nagai
Tatsuo
T
Teikyo University School of Medicine, Tokyo, Japan.
Arinuma
Yoshiyuki
Y
Yanagida
Tamiko
T
Yamamoto
Kazuhiko
K
Hirohata
Shunsei
S
D001323:Autoantibodies / Q000276:immunology*; D018929:Cell Culture Techniques; D018604:Epitope Mapping; D000939:Epitopes; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology; D012269:Ribosomal Proteins / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation
D001323:Autoantibodies; D000939:Epitopes; C489017:FCGR1A protein, human; D015850:Interleukin-6; D017452:Receptors, IgG; D012269:Ribosomal Proteins; D014409:Tumor Necrosis Factor-alpha