title: Combined IgG2, IgG4 and IgA deficiency: low C1q concentrations and the presence of excess C1r and C1s in an adult patient with recurrent pneumococcal infections.
abstract: The complement (C) profile was investigated in an adult patient with combined IgG2, IgG4 and IgA deficiency and recurrent pneumococcal infections. The analysis revealed no gross impairment of the classic and alternative pathways of C activation. However, the concentrations of circulating C1q were persistently decreased, and the sera contained an excess of C1r-C1s complexes, resembling the C1 aberrations previously found in children with recurrent acute otitis media. The concentrations of C4 in the patient were persistently low. This could be ascribed to partial C4 deficiency with lack of C4A variants. The patient's IgG and IgM antibody responses to pneumococcal capsular polysaccharides and to other bacterial carbohydrate antigens were very poor. Interestingly, pneumococcal C-polysaccharide (CPS) could be detected in serum obtained during infection-free periods. Since CPS has been shown to bind C1q without causing C1 activation, the possibility was considered that the C1 aberrations in serum were due to circulating CPS. After administration of intramuscular gammaglobulin to the patient, the serum C1q levels were observed to return to normal.
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000032:analysis; D002097:C-Reactive Protein / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003166:Complement Activating Enzymes / Q000032:analysis* / Q000172:deficiency*; D015922:Complement C1q; D015923:Complement C1r; D003173:Complement C1s; D003181:Complement C4 / Q000235:genetics; D003165:Complement System Proteins / Q000032:analysis; D004406:Dysgammaglobulinemia / Q000150:complications; D005260:Female; D006801:Humans; D017098:IgA Deficiency; D017099:IgG Deficiency; D007126:Immunoglobulin Allotypes / Q000235:genetics; D010035:Otitis Media, Suppurative / Q000097:blood; D011008:Pneumococcal Infections / Q000150:complications / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000097:blood; D013997:Time Factors; D005719:gamma-Globulins / Q000008:administration & dosage
chemical_list: D000907:Antibodies, Bacterial; D003181:Complement C4; D007126:Immunoglobulin Allotypes; D011135:Polysaccharides, Bacterial; D005719:gamma-Globulins; C027158:polysaccharide C-substance (Streptococcus); D015922:Complement C1q; D003165:Complement System Proteins; D002097:C-Reactive Protein; D003166:Complement Activating Enzymes; D015923:Complement C1r; D003173:Complement C1s