Quantitative Abnormalities of Allotypic Genes in Families with Primary Immune Deficiencies

Abstract

Genetic antigens of human immunoglobulin G (Gm factors) were measured in members of the families of selected patients with primary immunodeficiency. The sera of seven out of 27 heterozygous relatives had either deficient concentrations of one Gm allotype or an unbalanced ratio of Gm(f)/Gm(a). Since these markers for allelic IgG1 genes are found in almost equal amounts in normal heterozygous persons, the results suggested that there was a quantitative deficiency in the expression in serum of one Gm gene. In several families allotype abnormalities were found in three successive generations; in one instance the quantitative defect appeared to segregate independently of the Gm genes. The experimental data failed to support a recessive gene hypothesis, in that too few of the close relatives had evidence indicating that they were carriers of defective Gm genes. The results were interpreted as consistent with an inherited regulatory defect in certain families with this disorder.

A biased Gm haplotype and Gm paraprotein allotype in multiple myeloma suggests a role for the Gm system in myeloma development

“…The incidence of the G1m(f) allotype (86%) among IgG1 paraproteins was sixfold higher than that of the G1m(a) allotype, while the ratio of these allotypes in a healthy population in Serbia was 2.8 (Nikolić et al ., 1987). In other healthy populations, normal heterozygous persons have been found to have G1m(f):G1m(a) ratio of 1.17 (Litwin & Fudenberg, 1972) and 1.2 (Salier et al ., 1979), suggesting almost equal amounts of these markers for allelic IgG1 genes in those populations. Although class switching to Cγ1 has generally been found to occur on both alleles, the active and inactive one (Irsch et al ., 1993), the allotype‐associated differences within the Sγ1 might influence the IgG1 switching process, similarly to the differential switching between IgG3 (b) and (g) allotypes (Pan et al ., 1997).…”

Vitiligo and dysgammaglobulinemia. A case report and family study

“…In at least one instance, however, a quantitative immune defect segregated independently of Gm marker genes (Yount et a]. 1970, Litwin & Fudenberg 1972.…”

QUANTITATIVE STUDIES OF Gm ALLOTYPES II. G1m(1), G3m(5) AND G3m(21) IN SERA FROM HEALTHY CAUCASOID BLOOD DONORS, AND IN A FAMILY WITH THE INHERITANCE OF A GENE RESPONSIBLE FOR A WEAK Gm1, 17, 21, HAPLOTYPE

“…Except for the last one, all of these studies were carried out by the classical haemagglutination inhibition method on slides, which is not precise enough to show weak abnormalities. More recently, the use of an autoanalyser (Litwin, 1971) permitted accurate studies of Gm allotypes in sera from individuals with polyclonal hypergammaglobulinaemia (Litwin & Balaban, 1972) or from families with primary immune deficiencies (Litwin & Fudenberg, 1972).…”