Hyperimmunoglobulin G1(A1) Syndrome

The hyper-IgG1(A1) syndrome entails a polyclonal selective increase of the serum levels of immunoglobulin G1 and to a lesser extent of IgA1. Malignancy, infectious or autoimmune diseases and environmental agents do not seem to be responsible. Affected adults have chronic fatigue, high erythrocyte sedimentation rates, and significant levels of various autoantibodies. Hendriks et al. (1989) studied a family with 4 affected females in 3 generations. All affected individuals carried a particular immunoglobulin heavy chain allele distinguished by RFLP analysis; that allele was not present in unaffected family members. A 32:1 chance for linkage of this rare haplotype with the hyper-IgG1 syndrome in the family was interpreted by Hendriks et al. (1989) as indicating a dominant regulator located at the IgH locus which has a selective influence on the production of IgG1 (147100) and IgA1 (146900). They pointed to the findings of Oger et al. (1988) that in vitro lymphocyte immunoglobulin production levels on pokeweed stimulation behaved as a dominant trait. Krol-van Straaten et al. (1990), who like Hendriks and colleagues work in the Netherlands, questioned the existence of hyper-IgG1 syndrome as a separate entity. They stated that members of the family were known to their department and that one of them proved to have autoimmune hypothyroidism and a second delivered a baby with congenital heart block. They pointed to the report by Kay et al. (1988) of selectively increased polyclonal IgG1 levels associated with high titers of rheumatoid factors and antibodies to extractable nuclear antigens, notably SSA, in a subgroup of patients with connective tissue disease. See the reply by Hendriks et al. (1990).