Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

C1q and Complement Proteins Induce a Non-Caspase-Dependent, NonNecrotic, Cell Death, That Protects from Autoimmunity.

Atallah,  Mizhir, Grau,  Amir, Mevorach,  Dror

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of unknown etiology characterized by the presence of pathogenic high-titer autoantibodies to a diverse group of autoantigens. Eearly complement proteins are important in protecting humans against the development of SLE and the protective role of C1q and complement in SLE is mainly related to their role in clearance of dying cells. Since there are few other mechanism available for apoptotic cell clearance we were questioning whether C1q has unknown additional role that may lead to increased necrotic debris found in patients with SLE. Using spontaneous human neutrophil apoptosis in the presence of complement deficient sera we show that by 12h incubation with C1q-deficient serum there were 61.28%± 14.51% viable cells compared with 46.1%± 14.88% in autologous serum. Furthermore, there were more than three-fold higher rate of necrotic cells (p<0.001) when cells were incubated in autologous serum in comparison with C1q-deficient serum. We further characterized complement induced cell death by electron microscopy and caspase inhibitors to concluded that complement induced apoptotic, non-necrotic, non-caspase-dependent neutrophil death.

We further injected dying cells in the presence and absence of C1q and were able to show that in the absence of C1q, a lupus-like disease was developed whereas in the presence of C1q lupus-like disease was much milder (0.001) as judged by the development of immunoglobulins, autoantibodies, and kidney disease. Taken together, we conclude that C1q induced a non caspase-dependent cell death that is protected from necrosis and avoids autoimmunity. This is a novel role for C1q that was thus far suggested to have a role only in clearance of apoptotic cells. This observation and may add a new explanation for the presence of elevated necrotic debris in SLE patients.

To cite this abstract, please use the following information:
Atallah, Mizhir, Grau, Amir, Mevorach, Dror; C1q and Complement Proteins Induce a Non-Caspase-Dependent, NonNecrotic, Cell Death, That Protects from Autoimmunity. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :491
DOI: 10.1002/art.28260

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