LINKAGE OF IGA DEFICIENCY TO GM ALLOTYPES - THE INFLUENCE OF GM ALLOTYPES ON IGA-IGG SUBCLASS DEFICIENCY

IgA deficiency (IgAD) is the most common immunodeficiency, characteriz ed by an arrest in B cell differentiation. It has a sporadic occurrenc e or variable inheritance pattern, and is also linked to the HLA genes . IgA deficiency is sometimes associated with IgG subclass deficiency. In this study the Gm allotypes, as genetic characteristics of the IgG 1, IgG2 and IgG3, were analysed in 83 Caucasian IgAD individuals. Half of the patients presented with IgG4 < 0.01 g/l compared with 5% (P < 0.001) in a healthy population. Three of the 83 had significantly low IgG2 and four had significantly low IgG3 levels. Gm allotype frequenci es in IgAD deviated compared with a normal population. Of the 83 patie nts, 44 (53 %) showed homozygous G2 m('','') expression on the IgG2 lo cus (33% in controls, P < 0.01). In IgAD the Gm(a,'',g) haplotype was more frequent (43%) compared with controls (31%, P < 0.01). The Gm hom ozygous phenotype Gm(a,'',g/a,'',g) was most common, found in 20 of 83 patients (24%, P < 0.05) compared with controls (14%). On the other h and the Gm(f,n,b) haplotype of IgAD was rare (28%) compared with contr ols (45%, P < 0.001). The low IgG4, < 0.01 g/l, found in 50% of the pa tients, was even more frequent (56-69%) among the G2m('','') phenotype s. IgG subclass levels were given for different Gm phenotypes of the I gAD group and compared with controls. Significantly low IgG4 was revea led in the Gm(a,'',g/a,'',g) phenotype (P < 0.01) and significantly lo w IgC2 in the Gm(a,'',g/f,'',b) phenotype (P < 0.01). The Gm(a,'',g/f, '',b) phenotype contained the three patients found with IgG2 levels 4 < -2 s.d., and the four patients with IgG3 levels < -2 s.d. were prese nt among those with the homozygous Gm(a,'',g/a,'',g) phenotype; both p henotypes with G2 m('','') on the IgG2 locus. The 'compensatory' incre ase of IgG was significant for both IgG1 and IgG3 in all Gm phenotypes , but in the Gm(a,'',g/f,'',b). Thus, the susceptibility of IgAD with the additional IgC antibody deficiencies, down-regulated IgG4 and IgG2 /IgG3, is associated with Gm allotypes, especially the homozygous G2 m ('','') expression on the IgG2 locus.