Immunoglobulin G abnormalities in HIV-1 infected individuals with lymphoma.
BACKGROUND
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.


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
These findings indicate that subclass analysis to defined viral antigens may be a means to detect immune dysregulation in tumor development.
Lundholm
P
P
Swedish Institute for Infectious Disease Control, Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Lucht
E
E
Svedmyr
E
E
Rudén
U
U
Linde
A
A
Wahren
B
B
D000915:Antibody Affinity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007132:Immunoglobulin Isotypes / Q000097:blood; D007958:Leukocyte Count; D016483:Lymphoma, AIDS-Related / Q000097:blood* / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; C059762:HIV envelope protein gp120 (305-321); D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D010446:Peptide Fragments; D010455:Peptides; D011994:Recombinant Proteins