Reply to Woodruff et al.: C1q and C3-dependent complement pathway activation does not contribute to disease in SOD1 mutant ALS mice

Abstract

Three initiating pathways of the complement system of the innate immune system are generally recognized as the classic (activated by C1q), alternative, and lectin pathways. C3 is a central component common to all three pathways (1). Because induction of complement components had been identified in amyotrophic lateral sclerosis (ALS) patient samples and multiple rodent models that develop paralysis from each of three ALS-causing mutations in superoxide dismutase (SOD1), these discoveries led to our study (2) assessing the contribution to disease of two complement components in SOD1 mutant mice. We focused initially on C1q because our laser-microdissection had identified C1q induction within motor neurons during disease of multiple ALS mice. We then applied a more general test, determining the effects on disease from deletion of C3. The outcomes were unambiguous: neither C1q nor C3 deletion ameliorated disease course in two lines of ALS model mice.