HETEROZYGOUS AND HOMOZYGOUS FACTOR-H DEFICIENCY STATES IN A DUTCH FAMILY

Factor H, a 150-kD protein, is an important down-regulating protein of the alternative pathway of the complement system. Presently, only 15 persons, representing seven families, have been described with homozyg ous factor H deficiency. Deficiency of this protein, inherited as an a utosomal recessive trait and resulting in uncontrolled breakdown of C3 , results in depletion of components of the alternative pathway (facto r B, properdin) and of the terminal pathway (C5), and is associated wi th the onset of bacterial infections, glomerulonephritis and systemic lupus erythematosus (SLE). The proband of the family in this study suf fered from subacute cutaneous lupus erythematosus and had had meningoc occal meningitis due to serogroup X. She had a complete factor H defic iency at the protein level as determined by Western blotting. Among 21 relatives of the proband studied, encompassing three generations, 10 had low factor H levels, including the two children of the proband, in dicating a heterozygous factor H deficiency stale. In serum samples of the proband and 11 relatives prospectively studied, a strong correlat ion of factor H levels with C3, C3 haemolytic activity, factor B and p roperdin levels (P < 0.0001) was found. Alternative pathway protein le vels were significantly lower (Mann-Whitney test; Z values 3.6-2.7) in sera from the four heterozygous relatives studied than in sera from t he seven non-deficient relatives. In addition, a defect of the 37/42-k D H-related protein was found in the proband and two of 21 relatives, compared with four of 40 controls. A defect of the 24/29-kD H-related protein was present in one of 21 relatives studied and in none of the 40 controls.