Complement factor 2 deficiency: serological family study

Inherited complement deficiencies are associated with a variety of connective tissue diseases. A family with inherited deficiency of complement factor 2 (C2) is described in which two family members with homozygous C2 deficiency developed cutaneous vasculitis and siccasyndrome. The otherfamily members had heterozygous C2 deficiency and each member had the HLA-A25, B18, DR2 (w15) haplotype. The mother had seropositive rheumatoid arthritis. Further studies showed the presence of cryoglobulins, antibodies against endothelial celis, and anticardiolipin antibodies. (Ann Rheum Dis 1992; 51: 1254-1256) Complement factor 2 (C2) deficiency is the most common inherited complement deficiency. In white populations heterozygous C2 deficiency occurs in 1-2% and homozygous deficiency in 1 in 10 000 subjects.' 2 Agnello described the occurrence of autoimmune or lymphomatous diseases in 61% of patients with homozygous and 13% of patients with heterozygous C2 deficiency;' systemic/discoid lupus erythematosus, lupus-like disease, Henoch-Schonlein purpura, or polymyositis are the most commonly described diseases.3 We describe here two family members with homozygous C2 deficiency and three other members with heterozygous C2 deficiency. a clinical and Ronald Asherson, Munther Khamashta, neutrophil cytoplasmic antibody levels, antibodies to streptolysin 0, and viral serology including hepatitis A and B were negative or normal. Immune complex concentrations were increased at 147 mg IgG/l, (normal <49). Rheumatoid factor was positive with a RoseWaaler titre of >1/4096. IgG anticardiolipin antibodies were positive at 14-4 U/ml (normal <5 0). Cryoglobulins were detected with a cryocrit of 2%. The precipitate dissolved completely on warming to 37°C and reappeared on cooling to 4°C. Immunofixation of the cryoprotein showed the major component to be polyclonal IgG k (fig 2). Total haemolytic complement pathway concentrations were undetectable but alternate pathway, Clq, Clr, Cls, C3, and C4 concentrations were normal. Concentrations of C2 were undetectable, compatible with homozygous C2 deficiency. Her disease flared intermittently and the rheumatoid factor, immune complex, and cryoprecipitate concentrations followed the disease activity. Treatment with prednisolone by mouth (5-10 mg daily), azathioprine (100 mg Lupus Arthritis Research Unit, The Rayne Institute, St Thomas's Hospital, London SEI 7EH, United Kingdom D D'Cruz R Asherson M Khamashta G R V Hughes Department of Immunology, St Thomas's Hospital, London SEI 7EH, United Kingdom J Taylor T Ahmed Correspondence to: Dr Hughes. Accepted for publication 1 July 1992 Case reports