C3 dysregulation due to factor H deficiency is mannan-binding lectin-associated serine proteases (MASP)-1 and MASP-3 independent in vivo

Abstract

Uncontrolled activation of the complement alternative pathway is associated with complement‐mediated renal disease. Factor B and factor D are essential components of this pathway, while factor H (FH) is its major regulator. In complete FH deficiency, uncontrolled C3 activation through the alternative pathway results in plasma C3 depletion and complement‐mediated renal disease. These are dependent on factor B. Mannan‐binding lectin‐associated serine proteases 1 and 3 (MASP‐1, MASP‐3) have been shown recently to contribute to alternative pathway activation by cleaving pro‐factor D to its active form, factor D. We studied the contribution of MASP‐1 and MASP‐3 to uncontrolled alternative pathway activation in experimental complete FH deficiency. Co‐deficiency of FH and MASP‐1/MASP‐3 did not ameliorate either the plasma C3 activation or glomerular C3 accumulation in FH‐deficient mice. Our data indicate that MASP‐1 and MASP‐3 are not essential for alternative pathway activation in complete FH deficiency.