SERUM GM ALLOTYPE LEVELS IN COMMON VARIABLE IMMUNODEFICIENCY - PREPONDERANCE OF HOMOZYGOUS G2M('','') ON IGHCG2

Common variable immunodeficiency (CVI) is one of the most frequent pri mary immunodeficiency diseases, characterized by defective antibody fo rmation and associated with chronic sinopulmonary infections, autoimmu nity and malignancies. The genes for the constant heavy chains of IgG are located on chromosome 14 and were further studied by identifying a llelic, alternative Gm allotypes. These were defined by different epit opes for three of the IgG subclasses, G1m(a) and G1m(f) for IgG1, G2m( n) and G2m('') for IgG2 and G3m(g) and G3m(b) for IgG3. A sensitive co mpetitive ELISA method for quantitation of the Gm allotypes G1m(a), G1 m(f), G2m(n) and G3m(b) were used together with radial immunodiffusion IgG subclass quantitation. The dominating number of 25 of 33 patients (p < 0.001) expressed the homozygous G2m('','') allotype on IGHCG2 in combination with homozygous or heterozygous Gm allotypes on IGHCG1, a nd IGHCG3, namely Gm(f,f;'','';b,b), Gm(a,a;'','';g,g) and Gm(f,a;'',' ';b,g). Studies of Gm allotype quantities revealed a progressive seque ntial impediment of the programmed cascade. for downstream IGHCG gene rearrangements. According to the order of the IGHCG genes, the G3m all otype levels from the IGHCG3 were often normal, and G1m allotype level s from IGHCG1 were suppressed; G1m(a) was suppressed more than G1m(f), and most suppressed were G2m allotype levels from IGHCG2, both G2m(n) and G2m(''). The susceptibility of CVI is associated to G2m('','') ex pression from the IGHCG2 locus on chromosome 14, which has also been f ound in IgA IgG subclass deficiency, conditions known among first-degr ee relatives.