REVIEW - Thrombogenicity of TNF-alpha in RA defined through biological probes: TNF-alpha blockers

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Autoimmun Rev. 2004 Jun;3(4):261-6.

Thrombogenicity of TNF alpha in rheumatoid arthritis defined through

biological probes: TNF alpha blockers.

Ferraccioli G, Gremese E.

Division of Rheumatology, DPMSC, School of Medicine, University of

Udine, Udine 33100, Italy.

Abstract

Rheumatoid arthritis is a disease at high cardiovascular risk. It has

recently been shown that RA patients with more than 10 years disease

duration present a risk of myocardial infarction more than three times

higher than osteoarthritis controls. The major determinant is thought

to be the chronic inflammatory process, driven by some key cytokines

among which TNF alpha is thought to play the leading role in the

majority of the patients.

TNFalpha, therefore, once blocked by specific inhibitors like TNF

alpha blockers (Infliximab, Etanercept) should profoundly decrease the

cardiovascular risk. However, TNF blockers induce the appearance of

autoimmunity though in a small minority of the patients. This

autoimmunity is thought to be due to the poor clearance of apoptotic

bodies once the systemic inflammation (CRP, SAP) is controlled by the

specific blockers, and to the lack of control of some B cell

populations producing autoantibodies to specific autoantigens.

Among the autoantibodies arising during TNF blockade, anticardiolipin

appear to be the most crucial with respect to the cardiovascular risk.

The appearance of anticardiolipins at clinically significant levels

appears to be driven by two possible mechanisms, one due to common

infections of the urinary or upper airways tract during blockade of

soluble TNF alpha, the other due to the escape of some autoreactive B

cells during blockade of soluble and membranous TNF alpha.

Since both autoantibodies related to infections as well as the high

levels unrelated to infections, can be well controlled by appropriate

therapies, clinicians should pay attention to the biological

phenomenon before it becomes a clinical problem.

PMID: 15246021

http://www.ncbi.nlm.nih.gov/pubmed/15246021

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