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

Summary 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 C 3 activation through the alternative pathway results in plasma C 3 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 C 3 activation or glomerular C 3 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.