title: Homozygosity for the IgG2 subclass allotype G2M(n) protects against severe infection in hereditary C2 deficiency.
abstract: Homozygous C2 deficiency (C2D) is the most common deficiency of the classical complement pathway in Western countries. It is mostly found in patients with autoimmune disease or susceptibility to bacterial infections and in healthy persons. We wished to assess to what extent other immunological factors might explain differences of susceptibility to infections in C2D. For this reason, 44 Swedish patients with C2D were stratified with regard to the severity of documented infections. Investigations of IgG subclass levels, IgG subclass-specific GM allotypes, concentrations of factor B, properdin, and factor H, and polymorphisms of mannan-binding lectin and the Fc receptors FcgammaRIIa and FcgammaRIIIb were performed. Homozygosity for the G2M*n allele, which is known to promote Ab responses to polysaccharide Ags, was strongly associated with the absence of severe infections (p < 0.001) in the patients, suggesting a major protective role. The combination of mannan (or mannose)-binding lectin and C2 deficiency was found to be a minor susceptibility factor for invasive infection (p = 0.03). Low concentrations of IgG2 and factor B might sometimes contribute to susceptibility to infection. Other factors investigated did not appear to be important. In conclusion, the findings indicated that efficient Ab responses to polysaccharides are protective against severe infection in C2D. Implications with regard to vaccination should be considered.
authors.affiliation: Department of Infectious Diseases, University Hospital of Lund, SE-221 85 Lund, Sweden. goran.b.jonsson@skane.se
authors.forename: Göran
authors.initials: G
authors.lastname: Jönsson
authors.forename: Vivi-Anne
authors.initials: VA
authors.lastname: Oxelius
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Jean Henrik
authors.initials: JH
authors.lastname: Braconier
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sturfelt
authors.forename: Anders G
authors.initials: AG
authors.lastname: Sjöholm
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D016470:Bacteremia / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D001424:Bacterial Infections / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D002648:Child; D003175:Complement C2 / Q000172:deficiency* / Q000235:genetics*; D011415:Complement Factor B / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000145:classification / Q000235:genetics*; D007129:Immunoglobulin Gm Allotypes / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency / Q000235:genetics; D016920:Meningitis, Bacterial / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D008875:Middle Aged; D011018:Pneumonia, Pneumococcal / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D017452:Receptors, IgG / Q000235:genetics; D012720:Severity of Illness Index; D013296:Streptococcus pneumoniae / Q000276:immunology
chemical_list: D015703:Antigens, CD; D003175:Complement C2; C080568:Fc gamma receptor IIA; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D007129:Immunoglobulin Gm Allotypes; D037601:Mannose-Binding Lectin; D017452:Receptors, IgG; D011415:Complement Factor B