title: B cell depletion in HIV-1 subtype A infected Ugandan adults: relationship to CD4 T cell count, viral load and humoral immune responses.
abstract: To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001). HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb) titers against subtype A (p = 0.05) and subtype CRF02_AG (p = 0.02) viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02) and mean titer against the 10 viruses (p = 0.0002). In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001). These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection.
authors: Makerere University Walter Reed Project, Kampala, Uganda.
authors: Peter
authors: P
authors: Oballah
authors: Britta
authors: B
authors: Flach
authors: Leigh A
authors: LA
authors: Eller
authors: Michael A
authors: MA
authors: Eller
authors: Benson
authors: B
authors: Ouma
authors: Mark
authors: M
authors: de Souza
authors: Hannah N
authors: HN
authors: Kibuuka
authors: Fred
authors: F
authors: Wabwire-Mangen
authors: Bruce K
authors: BK
authors: Brown
authors: Nelson L
authors: NL
authors: Michael
authors: Merlin L
authors: ML
authors: Robb
authors: David
authors: D
authors: Montefiori
authors: Victoria R
authors: VR
authors: Polonis
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D008212:Lymphocyte Depletion; D008875:Middle Aged; D009500:Neutralization Tests; D011995:Recombination, Genetic / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014454:Uganda; D019562:Viral Load / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D015699:HIV Envelope Protein gp120