Hypoimmunoglobulinemia D: Frequency, family studies, and association with HLA

Abstract

The possible role of genetic factors controlling serum IgD levels was studied. A frequency plot of serum IgD levels in 372 blood bank donors revealed a non-Gaussian, apparently bimodal distribution. We therefore defined “low-serum IgD” as <0.002 mg/ml and “normal serum IgD” as ≥0.002 mg/ml. Among 1549 study subjects sub-sequently investigated, 95 had low serum IgD: 70 were unrelated, and 25 were in families with multiple low IgD cases. Among the 70 unrelated subjects with low serum IgD there was an increased frequency of HLA-B8 and A1, B8 when compared to their frequencies in normals and in 435 unrelated subjects with normal serum IgD. By immunofluorescence, IgD was present on the surface of lymphocytes in all individuals with either low or normal serum IgD. There was no correlation between serum IgD levels and the percentage of IgD-bearing cells. The mode of inheritance of low serum IgD was consistent with an autosomal recessive mode in 18 families. In 5 families the inheritance was consistent with a combination of multiple alleles affecting serum IgD levels. In the other 10 families either mode of inheritance could be invoked. These observations suggest that there are more than two alleles controlling serum IgD levels and that hypoimmunoglobulinemia D may be associated with certain HLA alleles.