title: Association between different anti-Tat antibody isotypes and HIV disease progression: data from an African cohort.
abstract: 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. 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.
  
  
  
  Anti-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.
  
  
  
  Anti-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).
  
  
  
  Anti-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.
authors.affiliation: Center for International Health, Ludwig-Maximilians-Universität München, Leopoldstraße 7, 80802, Munich, Germany. nclfnc1@unife.it.|Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. nclfnc1@unife.it.|Current address: CIMI INSERM U1135, 91 bd del'Hopital, 75013, Paris, France. nclfnc1@unife.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicoli
authors.affiliation: Center for International Health, Ludwig-Maximilians-Universität München, Leopoldstraße 7, 80802, Munich, Germany.|National Institute for Medical Research (NIMR)-Mbeya Medical Research Centre, Mbeya, Tanzania.
authors.forename: Mkunde
authors.initials: M
authors.lastname: Chachage
authors.affiliation: National Institute for Medical Research (NIMR)-Mbeya Medical Research Centre, Mbeya, Tanzania.|Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Clowes
authors.affiliation: National Institute for Medical Research (NIMR)-Mbeya Medical Research Centre, Mbeya, Tanzania.|Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.
authors.forename: Asli
authors.initials: A
authors.lastname: Bauer
authors.affiliation: National Institute for Medical Research (NIMR)-Mbeya Medical Research Centre, Mbeya, Tanzania.
authors.forename: Dickens
authors.initials: D
authors.lastname: Kowour
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cafaro
authors.affiliation: National Institute for Medical Research (NIMR)-Mbeya Medical Research Centre, Mbeya, Tanzania.
authors.forename: Leonard
authors.initials: L
authors.lastname: Maboko
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.|German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gavioli
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.|German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Saathoff
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany.|German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Geldmacher
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015483:HIV Antibodies / Q000145:classification*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007075:Immunoglobulin M / Q000032:analysis / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D013636:Tanzania; D019562:Viral Load; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: Antibodies; Clade B HIV; Clade C HIV; Diseases progression; Immune activation; Tat