Suppressed G2m(n) levels from IGHCG2 in IgA deficiency.
The aim of the study was to investigate the production of IgG from alternative alleles of IGHCG1, IGHCG2 and IGHCG3, closely related to IGHCA1 and IGHCA2 on chromosome 14, in IgA deficient (IgAD; serum IgA levels < 0.05 g/l) for individuals. Sixty-two IgAD individuals were included in the study and sera were investigated with the sensitive competitive indirect ELISA for measuring serum concentrations of the Gm allotypes G1m(a), G1m(f), G2m(n) and G3m(b), performed with specific monoclonal antisera and purified myeloma proteins in combination with IgG subclass quantitation. The known 'compensatorily increased' serum levels of IgG1 and IgG3 were recognized with significantly increased G1m(a) and G1m(f) from IGHCG1 and significantly increased G1m(g) and G3m(b) from IGHCG3. The quotients of G1m(a)/G1m(f) from IGHCG1 and G3m(g)/G3m(b) from IGHCG3 were also normal. Instead, the levels of G2m(n) from IGHCG2 were selectively decreased in combination with normal or increased levels of G2m(") from the same IGHCG2. The quotient G2m(n)/G2m(") was also significantly decreased. As the selectively decreased G2m(n) allotype expression from IGHCG2 was situated close to the non-expressing IGHCA1, the origin of most serum IgA could be the result of a defective common regulating factor. The selectively decreased G2m(n) allotype levels from IGHCG2 must also be discussed with a view to Gm allotype suppression described in mice. The selectively decreased G2m(n) allotype levels in G2m(n,") heterozygous IgAD individuals could be the result of a preferential allelic exclusion of G2m(n) favoring G2m(") on IGHCG2 in many cells.
Oxelius
V A
VA
Department of Pediatrics and Clinical Immunology, University Hospital, Lund, Sweden.
D000483:Alleles; D006801:Humans; D017098:IgA Deficiency / Q000378:metabolism*; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis* / Q000145:classification* / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains