Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
TNF and Natural Atheroprotective Antibodies Against Phosphorylcholine: Implications for Biologics in RA.
Ajeganova, Sofia, Fiskesund, Roland, Hafstrom, Ingiäld, Frostegard, Johan
We have recently determined that natural antibodies against phosphorylcholine (anti-PC) are protection factors for cardiovasculardisease (CVD), where low levels of anti-PC independent of other risk factors increase the risk of CVD. Further, anti-PC is anti-inflammatory, inhibiting proinflammatory effects of inflammatory phospholipids. Levels of IgM anti-PC are low in individuals living a traditional life-style in New Guinea (where CVD and rheumatic diseases are very uncommon) as compared to a western population. We have hypothesized that an immune deficient state low levels of anti-PC predispose to chronic inflammatory diseases. TNF is of major importance not only in rheumatic disease but also in CVD, atherosclerosis and metabolic syndrome. We here determine the role of TNF and TNF-inhibition on anti-PC levels and anti-PC production. We compared effects by TNF-inhibitors with rituximab.
In vitro anti-PC production by B-cells isolated from peripheral blood was determined by ELISA after 6 days of cell culture. Two hundred fifteen RA patients, aged 57.9±12.4 years with a mean disease duration of 8.5 (515) years were investigated with a one year follow up. Of these patients, 60 were treated with etanercept, 60 with infliximab and 42 with adalimumab as the first biologic, furthermore, 53 patients were treated with rituximab. The patients were followed and blood sampled at 0, 3, 6 and 12 months.
TNF at 1 ng/ml was shown to drastically (more than tenfold) decrease anti-PC production in vitro (p<0.0001) without inducing apoptosis. Anti-TNF treatment induced a 26% increase in anti-PC after 12 months of treatment (28%, 27.8% and 22% on etanercept, infliximab and adalimumab respectively), p<0.0001, while rituximab decreased anti-PC levels by 14%, p=0.023. Non-responders had lower anti-PC levels at baseline than responders in both anti-TNF, p=0.007, and Rituximab-treated subjects, p=0.041.
TNF was demonstrated to inhibit anti-PC production, a finding which suggest a novel mechanism by which anti-PC IgM could be decreased. Anti-TNF treatment may decrease risk of CVD by raising anti-PC levels. The adverse effect of rituximab on anti-PC levels may influence CVD-risk negatively. If treatment with anti-PC could have a role in some patients with RA including non-responders to biologics deserves further investigations.
To cite this abstract, please use the following information:
Ajeganova, Sofia, Fiskesund, Roland, Hafstrom, Ingiäld, Frostegard, Johan; TNF and Natural Atheroprotective Antibodies Against Phosphorylcholine: Implications for Biologics in RA. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :88