Anti-ribosomal P protein antibody induces Th1 responses by enhancing the production of IL-12 in activated monocytes

Abstract

Autoantibodies to ribosomal P proteins (anti-P) are detected in 12-16% of patients with systemic lupus erythematosus (SLE), and have been found to be associated with some manifestations, 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 tumor necrosis factor-α and interleukin (IL)-6. It is also possible that anti-P might regulate other monocyte functions, including the regulation of T helper (Th) responses. The current study was therefore undertaken to explore the effects of anti-P on the induction of Th1 responses. Peripheral blood mononuclear cells (PBMC) from healthy donors were cultured with affinity-purified anti-P or control IgG. Highly purified monocytes were cultured with interferon (IFN)-γ in the presence of anti-P or normal IgG. Anti-P significantly enhanced the production of IFN-γ by PBMC. Of note, anti-IL-12 monoclonal antibodies almost completely abrogated the anti-P-mediated upregulation of the IFN-γ production of PBMC. Accordingly, anti-P significantly enhanced the production of IL-12 by activated monocytes. These results indicate that anti-P induce Th1 responses by upregulating 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 the promotion of Th1 responses.

Overexpression of methyl-CpG-binding protein 2 and autoimmunity: evidence from MECP2 duplication syndrome, lupus, MECP2 transgenic and Mecp2 deficient mice

“…Nonetheless, T H 1 effector cells and IFN-γ production within target tissue play an important role in organ damage in lupus, particularly in the onset and progression of glomerulonephritis (17). Indeed, autoantibodies against ribosomal P, which are associated with lupus nephritis, have been shown to induce IFN-γ production (18). …”

Anti‐ribosomal P protein: a novel antibody in autoimmune hepatitis

“…Reinforcing this possibility, previous studies have demonstrated that ribosomal P0 proteins are expressed on the surface of hepatoma cells and anti‐rib P antibodies can penetrate into live hepatoma cells and cause cellular dysfunction . Moreover, anti‐rib P has the capacity to react with activated human peripheral blood monocytes and enhance the production of tumour necrosis factor‐α, interleukin‐6 and interleukin‐12, thus inducing a Th1 immune response . In AIH, the role of Th1 immune response is well established, as IFN‐γ secreted by Th1 cells is the main mediator of tissue damage in this disease .…”

Antibodies as Mediators of Brain Pathology

“…In vitro , anti-P antibodies from patients with diffuse NPSLE can directly react with the surface of human peripheral blood monocytes, which results in TNF-α production [73]. Therefore, anti-P antibodies could be associated with auto antibody-mediating inflammation in the CNS through the mechanism of BBB rupture by monocyte-derived TNF-α with or without infiltration of activated macrophage into CNS [73]. Accordingly, anti-P antibodies might also activate the immune system, access the CNS, and directly damage neurons in SLE patients [48,73].…”