Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Antibodies against An HSP Epitope Suppress Autoimmune Arthritis by Modulation of Cytokine Regulation
Ulmansky, R., Moallem, E., Hershko, A., Meyuhas, R., Katzavian, G., Naparstek, Y.
We have previously shown that resistance to Adjuvant Arthritis (AA) is due to the presence of anti-heat shock protein (HSP) antibodies, directed at peptide 6, a 16 amino-acid surface epitope.
In this work we have studied the effect of antibodies against peptide 6 on various models of autoimmune arthritis and the mechanism of their anti-inflammatory effect.
Active vaccination with peptide 6 as well as passive vaccination with monoclonal anti-peptide 6 murine and chimeric monoclonal antibodies suppressed significantly murine adjuvant and collagen arthritis. Incubation of murine and human mononuclear cells with the protective antibodies induced the secretion of IL-10. The antibodies bound to a surface molecule on human cell membrane and induced upregulation of IL-10 mRNA, via a cAMP associated pathway. The level of anti peptide 6 antibodies in the serum of patients with rheumatoid arthritis was significantly lower than in healthy controls. We have recently developed a humanized anti-peptide 6 antibody devoid of immunogenic epitopes. This antibody has similar immunomodulatory effects as those of the murine and chimeric antibodies.
We conclude that HSP contains protective B-cell epitopes exposed on its surface, and that natural and acquired resistance to autoimmune arthritis is associated with the ability to develop an antibody response to these epitopes. These antibodies cross react with a macrophage surface receptor and modulate cytokine production. Lower levels of anti peptide 6 antibodies in patients with RA suggest that they play a role in protection against human autoimmune diseases as well. The monoclonal humanized anti-peptide 6 antibody, as well as active vaccination with peptide 6, may serve as new therapeutic tools for suppression of human arthritis by skewing the immune system selectively towards an anti-inflammatory response.
To cite this abstract, please use the following information:
Ulmansky, R., Moallem, E., Hershko, A., Meyuhas, R., Katzavian, G., Naparstek, Y.; Antibodies against An HSP Epitope Suppress Autoimmune Arthritis by Modulation of Cytokine Regulation [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1