ELEVATED SERUM LEVELS OF SOLUBLE CD23 (sCD23) AND INTERLEUKIN 6 (IL 6) ARE ASSOCIATED WITH SMALL NON-CLEAVED/BURKITT'S LYMPHOMAS IN HIV-INFECTED PERSONS.

86 We have previously reported (Yawetz et al,Blood 85:1843, 1995) elevated serum levels of sCD23 in HIV-infected persons who developed AIDS-associated B cell lymphomas. We have extended our earlier study to include a larger number of subjects, and to examine additional markers of B cell activation and/or isotype switching in concert with sCD23. All subjects were homosexual men enrolled in the Multicenter AIDS Cohort Study (MACS), and included 49 persons with AIDS-associated B cell lymphoma. Frozen aliquots of sera were obtained from the UCLA MACS repository, from visits which preceded the diagnosis of lymphoma. Controls included subjects with AIDS but no malignancies, matched by absolute CD4 T cell number (n=44), HIV-infected with absolute CD4 T cells > 500/mm3 (n=48), and HIV-uninfected (n=48). Sera were tested for sCD23, IL6, total IgE, IgG4, and soluble CD27 (sCD27). After a comparison of sCD23 kits, a kit from The Binding Site was found to be the best for replicating our previous sCD23 results in serum. Consistent with previous observations, serum sCD23 and sCD27 were elevated in the lymphoma group (p=0.01). Although the mean levels of IL 6 and IgE in the lymphoma group were higher, the differences between groups were not statistically significant. No direct correlations were seen between sCD23 and any of the other markers. Multivariate analysis comparing the lymphoma and AIDS/non-malignancy groups is currently underway. Analysis of all lymphoma subjects revealed an association between high sCD23 and detectable IL6 (chi square >15). Logistic analysis of lymphoma subjects divided by type showed that detectable levels of serum IL6 was a powerful predictor that an individual with elevated sCD23 would be of the small non-cleaved/BL (SNC/BL) type. This suggests that overproduction of sCD23 and IL6 may be important in driving B cell hyperactivation and increased isotype switching, which in turn, may increase the likelihood of a chromosomal translocation and development of Burkitt's-like lymphomas.