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Natural antibodies targeting phosphorylcholin as novel immunomodu | 519
Rheumatology: Current Research

Rheumatology: Current Research
Open Access

ISSN: 2161-1149 (Printed)

+44-20-4587-4809

Natural antibodies targeting phosphorylcholin as novel immunomodulative drug candidates in rheumatic diseases including systemic lupus erythematosus (SLE) and rheumatoid artritis (RA)


International Conference and Exhibition on Orthopedics & Rheumatology

August 13-15, 2012 Hilton Chicago/Northbrook, USA

Johan Frosteg�rd

Accepted Abstracts: Rheumatology & Orthopedics

Abstract :

We have demonstrated that natural antibodies targeting phosphorylcholine (anti-PC) are negatively and independently associated with development of atherosclerosis and risk of cardiovascular disease in human prospective cohorts. Mechanisms include anti-inflammatory properties, inhibition of scavenger-uptake of lipids and inhibition of cell death caused by inflammatory phospholipids. We hypothesize that impaired immune function with low levels of circulating natural protective antibodies (NAbs) directly contributes to inability to resolve chronic inflammation, is non-redundant and leads to disease. Therefore supportive immunotherapy aimed at increasing circulating levels of protective NAbs will be beneficial in several therapeutic settings. Recently, we have investigated the effects of tumor necrosis factor (TNF)-antagonists and an anti-CD20 inhibitor (rituximab) on circulating anti-PC IgM in 215 patients with RA during a prospective one year study. Treatment with anti-TNF induced a 26% increase in anti-PC levels after 12 months of treatment, p<0.0001, while rituximab decreased anti-PC levels by 14%, p=0.023. Most interestingly, the â�?�?non-respondersâ�? to treatment had lower anti-PC levels at baseline than â�?�?respondersâ�? in both anti-TNF, p=0.007 and Rituximab-treated subjects, p=0.041. We hypothesize that increasing the capacity to ameliorate inflammation by increasing levels of circulating anti-PC (via passive administration in combination with tumor necrosis factor antagonists (anti-TNF) or CD20 targeting antibodies (rituximab)) will lead to clinically relevant improvements (becoming a â�?responderâ�?) in patients with rheumatoid arthritis. We aim at providing answers, on the level of pre-clinical â�?�?proof of conceptâ�?, whether the anti-PC antibodies in RA are relevant as a novel biomarker and as a potential therapeutic in combination with anti-TNF /rituximab.

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