RESEARCH - Rejuvenating the immune system in RA

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Nat Rev Rheumatol. 2009 Oct;5(10):583-8.

Rejuvenating the immune system in rheumatoid arthritis.

Weyand CM, Fujii H, Shao L, Goronzy JJ.

Kathleen B. and Mason I. Lowance Center for Human Immunology and

Rheumatology, Emory University, Atlanta, GA 30322, USA.

cweyand@...

In rheumatoid arthritis (RA), the aging process of the immune system

is accelerated. Formerly, this phenomenon was suspected to be a

consequence of chronic inflammatory activity. However, newer data

strongly suggest that deficiencies in maintaining telomeres and

overall DNA stability cause excessive apoptosis of RA T cells,

imposing proliferative pressure and premature aging on the system.

Already during the early stages of their life cycle, and long before

they participate in the inflammatory process, RA T cells are lost

owing to increased apoptotic susceptibility. A search for underlying

mechanisms has led to the discovery of defective pathways of repairing

broken DNA and elongating and protecting telomeric sequences at the

chromosomal ends. Two enzymatic machineries devoted to DNA repair and

maintenance have been implicated. RA T cells fail to induce sufficient

amounts of the telomeric repair enzyme telomerase, leaving telomeric

ends uncapped and thus susceptible to damage. Of equal importance, RA

T cells produce low levels of the DNA repair enzyme ataxia

telangiectasia mutated and the complex of nucleoproteins that sense

and fix DNA double-strand breaks. The inability to repair damaged DNA

renders naive T cells vulnerable to apoptosis, exhausts T-cell

regeneration and reshapes the T cell repertoire. Therapeutic attempts

to reset the immune systems of patients with RA and prevent premature

immunosenescence should include restoration of DNA repair capability.

PMID: 19798035

http://preview.ncbi.nlm.nih.gov/pubmed/19798035

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