Anti-C1q autoantibodies amplify pathogenic complement activation in systemic lupus erythematosus
V. Michael Holers
V. Michael Holers
Published September 1, 2004
Citation Information: J Clin Invest. 2004;114(5):616-619. https://doi.org/10.1172/JCI22820.
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Commentary

Anti-C1q autoantibodies amplify pathogenic complement activation in systemic lupus erythematosus

Abstract

Patients with systemic lupus erythematosus (SLE) often develop glomerulonephritis (i.e., inflammation in the glomeruli of the kidney), commonly referred to as lupus nephritis. Patients with lupus nephritis typically have autoantibodies to the complement classical pathway protein C1q. Whether these anti-C1q antibodies play any role in the development of lupus nephritis has been unclear. In this issue of the JCI, a new study demonstrates that anti-C1q antibodies can amplify glomerular injury but only when they are bound within the glomerulus to C1q that has been already brought to that site by other types of glomerular-reactive autoantibodies . These studies are the first, to our knowledge, to provide a causal link between anti-C1q antibodies and target organ damage in SLE.

Authors

V. Michael Holers

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Figure 2

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Simplified schematic demonstrating mechanisms of activation of classical...
Simplified schematic demonstrating mechanisms of activation of classical and alternative pathways and generation of C3 convertases (light blue). The alternative pathway C3 convertase (green box) can be generated by the activity of the classical pathway C3 convertase C4b2a (yellow box) on C3, which results in C3b formation. This is called the alternative pathway amplification loop. In patients with C4 nephritic factors, autoantibodies react with the complex of C4b2a and keep it from being inactivated, thus generating more C3b than would normally occur. C3b* in the alternative pathway can originate from C3b generated by the classical pathway C3 convertase C4b2a.