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 homozygous
factor H deficiency. Deficiency of this
protein, inherited as an autosomal recessive trait and resulting in uncontrolled breakdown of C3, results in depletion of components of the alternative pathway (
factor B, properdin) and of the terminal pathway (C5), and is associated with the onset of
bacterial infections,
glomerulonephritis and
systemic lupus erythematosus (SLE). The proband of the family in this study suffered from subacute
cutaneous lupus erythematosus and had had
meningococcal meningitis due to serogroup X. She had a complete
factor H deficiency 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, indicating a heterozygous
factor H deficiency state. In serum samples of the proband and 11 relatives prospectively studied, a strong correlation of
factor H levels with C3, C3 haemolytic activity,
factor B and
properdin levels (P < 0.0001) was found. Alternative pathway
protein levels were significantly lower (Mann-Whitney test; Z values 3.6-2.7) in sera from the four heterozygous relatives studied than in sera from the seven non-deficient relatives. In addition, a defect of the 37/42-kD 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.