Anti-cell antibodies in exposed seronegative individuals with HIV type 1-neutralizing activity.
Despite repeated exposures to HIV-1, some individuals remain seronegative. This study reports that sera from a fraction of exposed seronegative (ESN) subjects showed HIV-neutralizing activity; 5 of 17 ESN sera and none of 17 controls neutralized two different HIV-1 primary isolates (range of neutralizing titers: 1/20 to 1/60). The neutralizing activity was associated with the IgG fraction of 4 of 4 neutralizing ESN sera. Moreover, in 11 of 17 and 9 of 17 ESN sera (but none of the control sera) we found antibodies against HLA class I and CD4, respectively. One of the ESN sera (EU22) neutralized efficiently the primary virus derived from the seropositive partner and showed a good broadly cross-reactive neutralization. Immunoadsorption of two IgG fractions from EU19 and EU22 on peripheral blood mononuclear cells (PBMC) removed virus-neutralizing antibodies. The correlations between the ESN status and neutralizing activity (p<0.05), anti-HLA antibodies (p<0.0002), and anti-CD4 antibodies (p<0.001) were statistically significant. However, there was no statistically significant correlation between neutralizing activity and either anti-HLA or anti-CD4 antibodies. It can therefore be said that exposure to HIV-1 without seroconversion is, in some individuals, associated with HIV-neutralizing antibodies (not directed against viral antigens) and/or with anti-cell autoantibodies, which are possibly specific for cellular antigens involved in the infection/entry process.
Lopalco
L
L
DIBIT and Infectious Diseases Clinic, San Raffaele Scientific Institute, Milan, Italy. lopalco.lucia@hsr.it
Pastori
C
C
Cosma
A
A
Burastero
S E
SE
Capiluppi
B
B
Boeri
E
E
Beretta
A
A
Lazzarin
A
A
Siccardi
A G
AG
D001323:Autoantibodies / Q000097:blood*; D015704:CD4 Antigens / Q000276:immunology; D005260:Female; D005838:Genotype; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007558:Italy / Q000453:epidemiology; D008297:Male; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D019713:Receptors, CCR5 / Q000235:genetics; D016036:Seroepidemiologic Studies
D001323:Autoantibodies; D015704:CD4 Antigens; D015483:HIV Antibodies; D006680:HLA Antigens; D007074:Immunoglobulin G; D019713:Receptors, CCR5