Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Antiribosomal P Protein Antibody Induces Th1 Responses by Enhancing the Production of IL-12 in Activated Monocytes
Nagai1, Tatsuo, Yanagida2, Tamiko, Hirohata1, Shunsei
Autoantibodies to ribosomal P proteins (anti-P) are detected in 1216% of patients with SLE, and have been found to be associated with a variety of manifestations of the disease, including lupus psychosis, nephritis and hepatitis. We have recently disclosed that anti-P react with activated human peripheral blood monocytes, and enhance their production of TNFa and IL-6. It is also possible that anti-P might regulate other monocyte functions, including regulation of helper T cell (Th) responses. It has been recently shown that serum levels of IL-12 and IFNg are higher in patients with lupus nephritis (LN) and peripheral cells from LN patients show a Th1 phenotype. The current study was therefore undertaken to explore the effects of anti-P on the induction of Th1 responses.
IgG anti-P were affinity-purified from sera of anti-P positive lupus patients. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with anti-P or control IgG in round-bottomed polystyrene tubes for 120 hours. Highly purified peripheral blood monocytes were cultured in a 96-well microtiter plate with IFNg in the presence of anti-P or control IgG for 120 hours. The concentrations of IFNg and IL-12 in the culture supernatants were measured using ELISA.
Anti-P significantly enhanced the production of IFNg by PBMCs, compared with normal IgG or IgG from SLE patients devoid of anti-P. Of note, the up-regulation of IFNg production by anti-P was abrogated by anti-IL-12 monoclonal antibodies. Accordingly, anti-P significantly enhanced the production of IL-12 by peripheral blood monocytes activated with IFNg.
These results indicate that anti-P induce Th1 responses by up-regulating the production of IL-12 by activated monocytes. The data therefore suggest that anti-P play an important role in the pathogenesis of SLE through promotion of Th1 responses.
To cite this abstract, please use the following information:
Nagai, Tatsuo, Yanagida, Tamiko, Hirohata, Shunsei; Antiribosomal P Protein Antibody Induces Th1 Responses by Enhancing the Production of IL-12 in Activated Monocytes [abstract]. Arthritis Rheum 2009;60 Suppl 10 :583