Primary C3 deficiency is an extremely rare autosomalrecessive disease, with fewer than 50 families described worldwide. Plasma and intracellular C3 are considered B-cell receptor (BCR) and T-cell receptor (TCR) costimulators, respectively, but their contribution to lymphocyte biology remains obscure, particularly in humans. Reduced plasma C3 can be caused not only by primary C3 deficiency, due to loss-of-function C3 mutations, but also by secondary C3 deficiency or C3 consumption, due to gain-of-function C3 mutations or due to mutations in C3 regulators such as complement Factor I (CFI). 1 We reasoned that comparing Band T-cell differentiation and function in primary and secondary plasma C3 deficiency might help to understand the role of plasma and intracellular C3 in adaptive immunity. We report the immunological features of lymphocytes from 9 individuals with low plasma C3 belonging to 6 families, with mutations causing primary or secondary C3 deficiency and, in some cases, chronic kidney disease stages 1 to 3 (see Fig E1, A, and Tables E1 and E3 in this article’s Online Repository at www.jacionline.org).
Strategische Forschungsbereiche und Zentren
- Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)