The Journal of Immunology, Vol 138, Issue 11 3731-3736, Copyright © 1987 by American Association of Immunologists
HTLV-III neutralizing antibody development in transfusion-dependent seropositive patients with beta-thalassemia
M Robert-Guroff, PJ Giardina, WG Robey, AM Jennings, CJ Naugle, AN Akbar, RW Grady and MW Hilgartner
Sera collected in New York in 1984 from 77 patients with homozygous
beta-thalassemia were assayed for antibodies to HTLV-III by ELISA and
Western blot techniques. Eight (12%) of the 66 hypertransfused thalassemics
were seropositive. Retrospective sera of these eight individuals were
examined by radioimmune precipitation (RIP), and assays for neutralization
of virus infectivity were performed. With seroconversion, antibodies to
viral envelope proteins appeared first and were correlated with development
of neutralizing antibody. Affinity purified gp120, the major envelope
glycoprotein of HTLV-III, blocked viral infectivity and absorbed
neutralizing antibody activity from a positive serum. Neutralizing antibody
titers mirrored antibody titers to gp120 by RIP. Antibody to gp120
sometimes occurred in the absence of neutralizing antibody, although the
reverse was not true. One thalassemia patient who exhibited antibody to
gp120 for 3 yr post- seroconversion failed to develop neutralizing
antibody, acquired the acquired immunodeficiency syndrome with central
nervous system involvement and lymphoma, and subsequently died. In
contrast, all other seropositive thalassemics possessed neutralizing
antibodies, and were asymptomatic or exhibited only lymphadenopathy. These
results indicate that gp120 elicits neutralizing antibodies in the course
of natural infection with HTLV-III. The relationship seen here between
neutralizing antibody and better clinical outcome needs to be verified by
additional studies.
