Immunoglobulin G abnormalities in HIV-1 infected individuals with lymphoma

Polyclonal B-cell activation precedes the occurrence of malignant B-cell clones. Several recent reports suggest a perturbed cytokine regulation in HIV-related lymphomagenesis and Epstein-Barr virus (EBV) involvement in approximately half of the cases with generalized lymphoma.

We investigated whether altered immunoglobulin properties would be detected by fine analysis of the immunoglobulin G (IgG) subclass patterns against HIV and EBV epitopes.

HIV-1 infected patients in early stage, late stage and with lymphoma were analyzed by ELISA for anti HIV and EBV IgG class and subclass antibodies. Avidity and affinity of the antibodies were studied. The lymphoma patients were also studied by PCR for EBV DNA in serum.

The total IgG reactivity to several HIV antigens was similar in the three patient groups. However, lymphoma patients had a more restricted subclass pattern with significantly lower IgG1 and IgG3 anti gp120 titers compared to other HIV-infected patients but good and persistent total IgG and IgG1 (excluding the gp120 antigen) reactivities in contradiction to their low CD4 counts. IgG4 reactivity was sparse, detectable to significant levels in the symptomatic group only. The observed relative affinity of the HIV-specific IgG and IgG1 of lymphoma patients was similar to that of asymptomatic and symptomatic patients. The subclass reactivity to the EBV peptide was similar in all groups but lymphoma patients with EBV DNA in serum exhibited significantly lower anti EBV peptide titers than those who were EBV DNA negative.

These findings indicate that subclass analysis to defined viral antigens may be a means to detect immune dysregulation in tumor development.