Abstract
BackgroundThe presence of IgG and IgM against Tat, an HIV protein important for viral replication and immune dysfunction, is associated with slow disease progression in clade B HIV-infected individuals. However, although Tat activities strictly depend on the viral clade, our knowledge about the importance of anti-Tat antibodies in non-clade B HIV infection is poor. The objective of this study was to investigate the association of different anti-Tat antibody isotypes with disease progression in non-clade B HIV-infected subjects and to study the relationship between anti-Tat humoral responses and immunological abnormalities.MethodsAnti-clade B and -clade C Tat IgG, IgM and IgA titers were assessed in serum samples from 96 cART-naïve subjects with chronic HIV infection from Mbeya, Tanzania, and associated with CD4+ T cell count, plasma viremia and CD4+ and CD8+ T cell phenotypes.ResultsAnti-Tat IgM were preferentially detected in chronic HIV-infected subjects with low T cell activation (p-value = 0.03) and correlated with higher CD4+ T cell counts and lower viral loads irrespective of the duration of infection (p-value = 0.019 and p-value = 0.037 respectively). Conversely, anti-Tat IgA were preferentially detected in individuals with low CD4+ T cell counts and high viral load (p-value = 0.02 and p-value < 0.001 respectively). The simultaneous presence of anti-Tat IgG and IgM protected from fast CD4+ T cell decline (p-value < 0.01) and accumulation of CD38+HLADR+CD8+ T cells (p- value = 0.029).ConclusionsAnti-Tat IgG alone are not protective in non-clade B infected subjects, unless concomitant with IgM, suggesting a protective role of persistent anti-Tat IgM irrespective of the infecting clade.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1647-3) contains supplementary material, which is available to authorized users.
Highlights
The presence of IgG and IgM against Tat, an human immunodeficiency virus (HIV) protein important for viral replication and immune dysfunction, is associated with slow disease progression in clade B HIV-infected individuals
Anti-Tat IgM and IgA are differently associated with CD4+ T cell count and plasma viremia To determine the association between anti-Tat antibody isotypes and CD4+ T cell count, we evaluated the frequencies of subjects with the different anti-Tat isotypes after stratification according to the immunological HIV
With this and with reports showing that anti-Tat antibodies elicited against Tat expressed by one HIV clade may recognize Tat from different HIV clades [43, 46,47,48], our data demonstrate that a high proportion of individuals with detectable anti-Tat antibodies were able to recognize both clade B and C Tat
Summary
The presence of IgG and IgM against Tat, an HIV protein important for viral replication and immune dysfunction, is associated with slow disease progression in clade B HIV-infected individuals. Previous studies showed that anti-Tat IgM and IgG, present in a Nicoli et al BMC Infectious Diseases (2016) 16:344 small proportion of HIV-infected individuals, are more frequently found in the asymptomatic stage of infection [17, 18] and in non-progressors [19] and are associated with maintenance of CD4+ T cell counts [20,21,22] and low viral load [23, 24] Most of these studies were conducted in clade B HIV-infected cohorts and with clade B Tat, whereas the effect of naturally occurring anti-Tat antibodies in non-clade B HIV infections has been poorly investigated and the relationship between anti-Tat humoral responses and the development of immunological abnormalities has not been reported.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
