All Over the Joint

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Science  05 Apr 2002:
Vol. 296, Issue 5565, pp. 17
DOI: 10.1126/science.296.5565.17a

Rheumatoid arthritis is a debilitating and costly disease that affects over 2 million people in the United States; it is characterized by chronic inflammation of the synovial lining of the joints, which can ultimately lead to destruction of the joint and surrounding tissue. This inflammation is thought to be an autoimmune reaction, and the glycolytic enzyme glucose-6-phosphate isomerase (GPI) has been fingered as a likely target antigen. However, GPI is expressed in all tissues, so it has been difficult to explain why the immune attack is directed specifically to the joints.

New insight into this puzzle emerges from Matsumoto et al., who show that in healthy mice, GPI from the bloodstream selectively accumulates on the cartilage surface lining the joints. These joint-specific deposits of GPI were greatly amplified in a mouse model of rheumatoid arthritis. In complementary work, also with mice, Wipke et al. found that systemically injected antibodies against GPI localize within minutes to the peripheral joints and that this localization persists for at least 24 hours. These results support a model in which GPI (or other target antigens) exposed on the cartilage surface serves as a target for pathogenic autoantibodies, which in turn trigger an inflammatory cascade that proceeds unimpeded because cartilage lacks the normal cellular inhibitors of antibody-triggered immune attacks.—PAK

Nature Immunol. 3, 360; 366 (2002).

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