Properdin deficiency was demonstrated in three generations of a large Swiss family. The concentration of circulating properdin in affected males was < 0.1 mg/l, indicating properdin deficiency type I. Two of the nine properdin-deficient males in the family had survived meningitis caused by Neisseria meningitidis serogroup B without sequel. Two point mutations were identified when the properdin gene in one of the properdin-deficient individuals was investigated by direct solid-phase sequencing of overlapping polymerase chain reaction (PCR) products. The critical mutation was found at base 2061 in exon 4, where the change of cytosine to thymine had generated the stop codon TGA. The other mutation was positioned at base 827 in intron 3. The stop codon in exon 4 was also demonstrated by standard dideoxy sequencing in three additional family members. The question was asked if genetic factors such as partial C4 deficiency and IgG allotypes could have influenced susceptibility to meningococcal disease in the family. No relationship was found between C4 phenotypes and infection. Interestingly, the two properdin-deficient males with meningitis differed from the other properdin-deficient persons in that they lacked the G2m(n) allotype, a marker known to be associated with poor antibody responses to T-independent antigens. This implies that the consequences of properdin deficiency might partly be determined by independent factors influencing the immune response.

Sjöholm, A. G. Complement Components in Normal Serum and Plasma Quantitated by Electroimmunoassay. Scand. J. Immunol. 4, 25-30, 1975. The concentrations of C1q, C1s, C3, C4, C5, C3 proactivator, and C1 inactivator in serum and EDTA plasma from 100 normal adults were determined by electroimmunoassay. The normal range of each of the proteins is given. The C1q values varied more closely with the C1s values than with the levels of the other complement components. C3, C5, and C3 proactivator seemed to form a fairly interdependent group. The reproducibility of double determinations (interplate variation) was 4.9% to 7.9%. The variation of the complement component levels on repeated sampling from normal individuals was investigated. Also, repeated freezeing and thawing and storage at room temperature of serum and plasma were studied for their effect on the quantitation of the complement components. C3 and C4 values obtained by electroimmunoassay were in agreement with the values obtained by single radial immunodiffusion.

A selective deficiency of properdin (P) was identified in a 58-year-old male and in his 29-year-old nephew, both of whom were clinically healthy. As determined by different immunochemical methods P at low concentrations (about 2 mg/1) was detectable in serum and plasma. Three female relatives, including the mother and daughter of one of the P- deficient males showed moderately low P concentrations. The findings clearly suggested that the deficiency was inherited as an X-linked trait. Three males belonging to another family with P deficiency also showed detectable P concentrations. By contrast, no P (<0.1 mg/1) was found in 8 males belonging to three other families. We suggest that there are two variants of X-linked P deficiency; P deficiency type 1, characterized by extremely low P concentrations (< 0.1 mg/1); and P deficiency type 2 recognizable by P concentrations of about 2 mg/1. The P detected in P deficiency type 2 had subunits of normal molecular weight (52 kilodal- tons), but eluted in a lower molecular weight range than did the P of normal serum, either on gel filtration (Ultrogel AcA 22) or on size exclusion chromatography (TSK-4000). The evidence suggested that the P concentration may be one determinant of P oligomer formation. P-deficient serum type 2 did not support fluid phase C3 cleavage in the presence of such alternative pathway activators as inulin and zymosan, nor did it support efficient lysis of guinea pig erythrocytes in agarose gel. By contrast, rabbit erythrocytes were efficiently lyzed, but at a slow rate. P-deficient serum type 1 did not support lysis of rabbit erythrocytes in the assay system used. The reaction was clearly promoted by very low concentrations of purified P. Partially purified P from a male with P deficiency type 2 was shown to be hemolytically active. Further evidence of P function in P deficiency type 2 was obtained by using IgG- presensitized serogroup W-135 meningococci in an alternative pathway-mediated serum bactericidal assay.

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