B cell depletion in HIV-1 subtype A infected Ugandan adults: relationship to CD4 T cell count, viral load and humoral immune responses

• Published in: PloS one Vol. 6; no. 8; p. e22653
• Main Authors: Oballah, Peter, Flach, Britta, Eller, Leigh A, Eller, Michael A, Ouma, Benson, de Souza, Mark, Kibuuka, Hannah N, Wabwire-Mangen, Fred, Brown, Bruce K, Michael, Nelson L, Robb, Merlin L, Montefiori, David, Polonis, Victoria R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.08.2011; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adolescent; Adult; Adults; AIDS; Antibodies; Antibodies, Neutralizing - immunology; Antibody-Dependent Cell Cytotoxicity - immunology; B cells; B-Lymphocytes - immunology; Binding; Biology; Care and treatment; Case-Control Studies; CD4 antigen; CD4 Lymphocyte Count; Chronic infection; Comparative analysis; Correlation; Depletion; Glycoprotein gp120; HIV; HIV Envelope Protein gp120 - immunology; HIV Infections - blood; HIV Infections - immunology; HIV Infections - virology; HIV-1 - classification; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immune response; Immune response (humoral); Immunity, Humoral - immunology; Infections; Lymphocyte Depletion; Lymphocytes B; Lymphocytes T; Medical research; Medicine; Middle Aged; Neutralization; Neutralization Tests; Patients; Recombination, Genetic - genetics; T cell receptors; T cells; T-Lymphocytes, Helper-Inducer - immunology; Uganda; Vaccines; Viral Load - immunology; Viruses; Young Adult; Uganda; United States > US; Maryland; Kampala Uganda; Tanzania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022653

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.