- Paper Report
- Open Access
Therapeutic potential of TACI-Ig in treatment of arthritis
- Virginia Smith Shapiro1
© Biomed Central Ltd 2001
- Received: 10 October 2001
- Accepted: 6 November 2001
- Published: 15 November 2001
BLyS (BAFF, TALL-1, THANK, zTNF4) and APRIL are members of the TNF family that modulate B-cell activation and survival. TACI and BCMA are two previously characterized receptors for BLyS that also bind to APRIL. Transgenic animals that overexpress BLyS develop symptoms similar to SLE. Recombinant TACI-Ig decreases disease severity and frequency in SLE susceptible mice, thus, implicating BLyS in the development of SLE and, perhaps, autoimmune disorders in general. Elevated levels of BLyS are also observed in the serum of RA patients. In this study, the effect of TACI-Ig on arthritis in a mouse model of CIA was examined.
Injection of TACI-Ig prior to the second collagen injection in male DBA/1 mice delayed the onset and decreased the severity of disease and decreased the percentage of animals that developed CIA. To determine the effects of TACI-Ig in a manner resembling treatment of existing disease, TACI-Ig treatment initiation was delayed until 7 days after the second injection, when 52% of the animals developed anticollagen antibodies and demonstrated signs of inflammation. Again, TACI-Ig treatment inhibited disease progression, decreasing both inflammation and the percentage of animals that progressed to established disease. Thus, TACI-Ig is a novel therapeutic agent for autoimmune disease, including arthritis, with great clinical potential. In both TACI-Ig transgenic and BLyS-deficient mice decreases in mature B cells were observed, implicating BLyS in B-cell development. However, TACI-Ig injections into normal mice caused a significant decrease in the number of mature B cells, although immature B-cell populations were unaffected.
CIA model, gene targeting, knockout mice, transgenic mice
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