Aberrant and unstable expression of immunoglobulin genes in persons infected with human immunodeficiency virus

We examined the IgM V-H gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM V-H gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM V-H gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig V(H)3 genes and frequently displayed marked fluctuations in the relative expression levels of this V-H gene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig V(H)3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig V-H gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM V-H gene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens. (C) 1998 by The American Society of Hematology.