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Abstract: Role of complement in the development of autoimmunity

  [ 13 votes ]   [ Discuss This Article ]
www.ProHealth.com • November 1, 2002


Curr Dir Autoimmun 2003;6:154-68  Boackle SA, Holers VM.  University of Colorado Health Sciences Center, Denver, Colo., USA. susan.boackle@uchsc.edu

B cell complement receptors have been shown to be important in the generation of normal humoral immune responses, and they likely also participate in the development of autoimmunity. Complement component and receptor deficiencies have been associated with SLE in both animal models and patients with disease. Recent data suggest that Cr2 is a lupus susceptibility gene in the NZM2410 mouse model for lupus, as it generates complement receptors that are structurally and functionally altered. Complement deficiency may result in autoimmune disease because of the inability to appropriately clear immune complexes or apoptotic cells or by the impaired generation of C3-coated autoantigens for CR1/CR2.

In turn, CR1/CR2 may participate in the maintenance of B cell tolerance by lowering the threshold for negative selection of autoreactive B cells, by targeting autoantigen to FDCs in secondary lymphoid organs, or by regulating autoreactive T cell function. The effect of CR2 has not been dissected from that of CR1 in the animal studies performed to date. Furthermore, the effects of CR1/CR2 dysfunction or partial deficiency, which are found in the NZM2410 mouse model and in patients with SLE respectively, have not been delineated from those of complete deficiency, which has been studied in several animal models of autoimmunity and tolerance.

Although CR1/CR2 dysfunction or deficiency may confer only a modest phenotype in isolation, it is likely that when combined with other disease susceptibility genes it will result in a fully penetrant end-stage disease phenotype. Understanding the mechanisms by which these receptors participate in the maintenance of B cell tolerance will be critical in developing appropriate therapeutic interventions for patients with autoimmune diseases such as SLE.

PMID: 12408051 [PubMed - in process]




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