Publication:

Inherited dysregulation of the complement system (2004)

Author(s): Goodship THJ

    Abstract: In recent years there has been a substantial increase in the understanding of the genetics and pathogenesis of HUS. Mutations in factor H, a fluid-phase regulator of the alternative complement pathway, have been identified in 15-30% of patients with both familial and sporadic (D-) HUS. The mutations mainly cluster in the C terminal part of factor H, a region that is important for both binding to c3b and also polyanionic structures on cell surfaces. This leads to loss of protection against complement mediated endothelial injury. Mutations in the membrane bound complement regulator, membrane cofactor protein (MCP; CD46) have also been described in three families. These result in an impairment of inactivation of surface bound c3b. Finally mutations in the serine protease, factor I that lead to deficiency of the protein have been reported in two HUS patients. There is therefore now overwhelming evidence that dysregulation of the alternative complement pathway predisposes to the development of a thrombotic microangiopathy

    Notes: TY - JOUR DA - 20041223 IS - 0377-8231 LA - eng PT - Journal Article SB - IM RP - NOT IN FILE

      • Journal: Bulletin et Memoires de le Academie Royale de Medecine de Belgique
      • Volume: 159
      • Issue: 2
      • Pages: 195-198
      • Publisher: Academie Royale de Medecine de Belgique
      • Publication type: Article
      • Bibliographic status: Published
      Staff

      Professor Tim Goodship
      Professor of Renal Medicine