Faculty Bibliography

Serum IgD levels in individuals infected with the human immunodeficiency viruses (HIV) were studied as a means of monitoring the character and timing of B cell activation in individuals with this infection. Significantly increased levels of IgD were characteristic of homosexual men who were HIV seropositive but asymptomatic or mildly symptomatic. The hyper IgD globulinaemia became progressively more pronounced in patients with increasingly severe infection and reached its most marked level in patients with AIDS-related complex (ARC). In ARC patients, IgD levels were increased 8.8-fold above normal which was disproportionately greater than the 2.4-fold increase in IgG, the 1.8-fold increase in IgA and the 1.6-fold increase in IgM. IgD levels declined in AIDS patients (although remained elevated compared to controls). The data suggest that an unusual type of B cell activation is responsible for the unique pattern of hypergammaglobulinaemia seen in this disease and that the B cell activation occurs early in the pathogenesis of HIV infection, often before development of symptoms, and continues throughout the course of infection

Blood specimens from 165 intravenous drug users who were seropositive for the human immunodeficiency virus (HIV), from 158 seropositive homosexual men with lymphadenopathy, and from 77 patients with acquired immunodeficiency syndrome (AIDS) were assessed immunologically. Immunologic parameters were analyzed by the Guttman scalogram technique to determine if immunologic abnormalities occurred in a nonrandom pattern. The following four patterns emerged: (i) seropositivity for HIV with no immunologic abnormalities; (ii) seropositivity for HIV with a depressed T4/T8 cell ratio; (iii) seropositivity with a depressed T4/T8 cell ratio and T4-cell depletion; and (iv) seropositivity with a depressed T4/T8 cell ratio, T4-cell depletion, and lymphopenia. Ninety-two to 100% of subjects in each of the three groups of patients were found \'to scale\' because the abnormalities occurred in the cumulative, ordered fashion described. This nonrandom occurrence of abnormalities indicates an ordered progression of immunologic abnormalities in individuals infected with HIV, a finding useful in the staging of both symptomatic and asymptomatic HIV-seropositive subjects.

Serum samples from 24 patients with acquired immune deficiency syndrome (AIDS) and from 15 patients with an early or milder form of this disease (\'suspected AIDS\') were found to contain elevated levels of beta 2-microglobulin (beta 2M). Therefore, prospective studies of 40 asymptomatic homosexual men from New York City were undertaken to determine whether quantitation of beta 2M and other immunologic variables was useful in recognizing those in populations at high risk for this disease who have a high probability for experiencing symptoms consistent with AIDS. After 20 to 26 months of follow-up, two of those persons now have AIDS and four have suspected AIDS. All six of these persons had elevated serum beta 2M levels and other immunologic abnormalities when they entered this study. Of those tested, only one other man had an increased level of beta 2M; neither he nor any of the remaining 33 persons in this group developed AIDS.

The cases of 20 male homosexuals with Kaposi\'s sarcoma and the acquired immunodeficiency syndrome were compared with those of 40 age- and race-matched male homosexual controls. Patients with Kaposi\'s sarcoma had lower OKT4/OKT8 (T-helper/T-suppressor) ratios than controls, due to smaller numbers of OKT4 cells. Serum IgG concentrations and antibody titers to cytomegalovirus in patients exceeded those in controls, but patients had lower antibody titers to Epstein-Barr virus. Logistic regression analysis comparing patients with controls showed significant relative risks for Kaposi\'s sarcoma associated with the number of partners per month in receptive anal-genital intercourse, occasions per month of \' fisting ,\' and cytomegalovirus antibody titers. Cytomegalovirus titers also were inversely correlated with OKT4 cell concentrations in the control group. Significantly greater OKT4 cell concentrations were found at diagnosis in HLA-DR5-positive patients than in HLA-DR5-negative patients. Patients who have HLA-DR5 may express disease at lesser degrees of immunodeficiency than HLA-DR5-negative patients.