REVIEW - Developments in the scientific understanding of RA

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Arthritis Research & Therapy 2009, 11:249doi:10.1186/ar2758

Published 14 October 2009

Developments in the scientific understanding of rheumatoid arthritis

Jörg J Goronzy and Cornelia M Weyand

Lowance Center for Human Immunology and Rheumatology, Department of

Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA

Abstract

Rheumatoid arthritis (RA) is recognized to be an autoimmune disease

that causes preclinical systemic abnormalities and eventually leads to

synovial inflammation and destruction of the joint architecture.

Recently identified genetic risk factors and novel insights from

animal models of spontaneous arthritis have lent support to the

concept that thymic selection of an autoreactive T-cell repertoire is

an important risk factor for this disease. With advancing age, defects

in the homeostatic control of the T-cell pool and in the setting of

signaling thresholds lead to the accumulation of pro-inflammatory

T-effector cell populations and loss of tolerance to neo-antigens,

such as citrullinated peptides. As the breakdown of tolerance to

modified self-antigens can precede synovitis by decades, repair of

homeostatic defects may open a unique window of opportunity for

preventive interventions in RA. The end result of RA, destruction of

cartilage and bone, appears to be driven by cytokine- and cell

contact-induced activation of synoviocytes and monocytic cells, some

of which differentiate into tissue-destructive osteoclasts. Targeting

mediators involved in this process has greatly improved the management

of this chronic inflammatory syndrome.

Read the full review here:

http://arthritis-research.com/content/11/5/249

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