Hereditary C7 deficiency. Diagnosis and HLA studies in a French-Canadian family.

Abstract

A B S T R A C T The serum of a 44-yr-old woman of French-Canadian descent having a B-27 positive ankylosing spondylitis was deficient in the seventh component of complement (C7) as determined by hemolytic and immunnochemical methods. No inhibitor against C7 was detected, and the levels of all other complement components were normal. No deficiency in the opsonic activity of the serum was found, and the results of basic coagulation studies of the plasma were normal. On investigation of the patient's family, two sisters were found to have the same deficiency but were otherwise in good health. The seven other siblings were heterozygous for C7 deficiency, while the paternal aunt had a normal C7 level. In the third generation, six children ofthe three homozygous sisters and five children of heterozygotes were available for testing. Studies of the HLA antigens in all the 22 subjects and in three spouses indicated no close linkage between the C7 deficiency and the HLA system. In addition, the simultaneous occurrence of two hereditary complement deficiencies (C2 and C7) was discovered in one family of this remarkable kindred.

Inherited Deficiency of the Seventh Component of Complement Associated with Nephritis

“…However, another family member with this haplotype showed normal levels of C7, and two of the five family members with one-half normal levels of C7 lacked this haplotype. Thus, despite the detection of a single haplotype at the HLA-A and HLA-B loci, it would seem that the genes coding for the C7 protein in this family, as in the family reported by Delage et al (16), were inherited independently of those coding for the HLA antigens, but additional studies are needed to confirm this interpretation.…”

“…Since complete family studies could not be obtained, the data presented does not exclude the possibility of a distant linkage between HLA and C7 on chromosome 6, because one recombinant event could account for the single family member studied (the proband's half-sister 111-9) with the HLA haplotype Aw24/B12 and normal levels of C7. However, evidence presented in the investigations of two other C7-deficient individuals (16,29) clearly showed a lack of linkage between HLA and C7, as clo recent studies on C7 polymorphism in man (30). C7 deficiency was first reported in an individual with sclerodactyly and telangiectasia (13), and then later in an apparently normal adolescent (14), a 44-yrold lady with ankylosing spondylitis (16), in several members of a family who have shown an unusual predisposition to gonococcal infections (11), and in a 28-yr-old lady (G. S.) with systemic lupus erythematosus.…”

“…Her physical examination was remarkable only for oculovascular changes characteristic of' hypertenisioni. The hemogram was normal, the erythrocyte sedimentation rate (WN'estergren) was 58 mm/h, and the C-reactive protein level was 16 ,ug/ml. Bone marrowv biopsy showed a hypocellular marrow which otherwise was normal.…”

“…One was a 42-yrold womian with Raynaud's phenomenon, sclerodactyly, and telangiectasia (13); a second was a healthy 12-yrold boy (14,15); and a third was a 44-yr-old woman (with two healthy homozygous siblings) with ankylosing spondylitis (16). In addition, a family with three members lacking C7 has recently been presented in 'Abbreviations used in this paper: BSA, bovine serum albumin, C, complement; EA, antibody-sensitized sheep erythrocytes; GGVB, GVB diluted with an equal volume of 5% glucose; GVB, veronal-buffered saline containing 0.1% gelatin; HLA, human leukocyte antigens; C7D, C7-deficient; C3B-INA, C3b-inactivator; C567-INH, C567-inhibitors.…”

Genetic control of the eighth component of complement.

“…Concordant inheritance of polymorphism of C6 and C7 and of a combined defect of C6 and C7 in families suggests the linkage of C6 and C7 (9,25). Studies of the polymorphism of C4 and the C4-deficiency state have led to the conclusion that C4 is linked to HLA (5-7, 26, 27) and corresponding studies of the relevant proteins that C3 (28), C5 (29,30), C6 (31,32), and C7 (33,34,10) are not closely linked to HLA. Two studies of the relationship of C8 deficiency to HLA in large families have been described (35,13).…”