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A protective role for innate immunity in systemic lupus erythematosus

Abstract

Clinical and genetic studies in humans and animal models indicate a crucial protective role for the complement system in systemic lupus erythematosus (SLE). This presents a paradox because the complement system is considered to be an important mediator of the inflammation that is observed in patients with SLE. One current view is that complement provides protection by facilitating the rapid removal of apoptotic debris to circumvent an autoimmune response. In this Opinion article, I discuss an alternative model in which complement — together with other components of the innate immune system — participates in the 'presentation' of SLE-inducing self-antigens to developing B cells. In this way, the complement system and innate immunity protect against responses to SLE (self) antigens by enhancing the elimination of self-reactive lymphocytes.

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Figure 1: Autoantibody-mediated pathogenesis of SLE.
Figure 2: Hypotheses for the association of SLE with genetic deficiencies.

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Acknowledgements

I thank past and present members of the laboratory for thoughtful discussions on the topic of innate immunity and B-cell tolerance. Research was supported by the National Institutes of Health, United States.

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DATABASES

Entrez Gene

C1q

C1r

C1s

C3

C4

C5

CR1

CR2

DNase I

MASP2

SAP

OMIM

SLE

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Michael Carroll's laboratory

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Carroll, M. A protective role for innate immunity in systemic lupus erythematosus. Nat Rev Immunol 4, 825–831 (2004). https://doi.org/10.1038/nri1456

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