title: Chronic HIV-1 Infection Induces B-Cell Dysfunction That Is Incompletely Resolved by Long-Term Antiretroviral Therapy.
abstract: OBJECTIVE
  To determine the effect of long-term antiretroviral therapy (ART) on HIV-1-induced B-cell dysfunction.
  
  
  METHODS
  Comparative study of ART-naive and ART-treated HIV-infected patients with non-HIV controls.
  
  
  METHODS
  B-cell dysfunction was examined in patients with HIV-1 infection (n = 30) who had received ART for a median time of 9.25 years (range: 1.3-21.7) by assessing proportions of CD21 B cells (a marker of B-cell exhaustion) and proportions of tumor necrosis factor-related apoptosis-inducing ligand or B and T lymphocyte attenuator B cells, and serum levels of immunoglobulin free light chains (markers of B-cell hyperactivation). The association of these markers with serum levels of IgG1 and IgG2, and production of IgG antibodies after vaccination with pneumococcal polysaccharides were also examined. ART-naive patients with HIV (n = 20) and controls (n = 20) were also assessed for comparison.
  
  
  RESULTS
  ART-treated patients had increased proportions of CD21 and tumor necrosis factor-related apoptosis-inducing ligand B cells and, furthermore, although proportions of B and T lymphocyte attenuator B cells were not significantly different from controls, they correlated negatively with CD21 B cells. Proportions of CD21 B cells also correlated negatively with current CD4 T-cell counts. In ART-naive patients with HIV, free light chains correlated with CD21 B cells and IgG1, but not IgG2. Serum IgG2:IgG1 ratios were substantially lower than normal in patients with HIV and did not resolve on ART. In ART-treated patients, IgG antibody responses to pneumococcal polysaccharides after vaccination were not associated with markers of B-cell dysfunction.
  
  
  CONCLUSIONS
  B-cell dysfunction persists in patients with HIV receiving long-term ART. The causes and consequences of this require further investigation.
authors.affiliation: *School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Australia;†Center for Vaccine and Infectious Disease Research, Telethon Kids Institute, The University of Western Australia, Perth, Australia;‡Department of Infectious Diseases, Prince of Wales Hospital, Sydney, Australia;§Prince of Wales Clinical School, University of New South Wales, Sydney, Australia;‖School of Paediatrics and Child Health, The University of Western Australia, Perth, Australia; and¶Department of Clinical Immunology, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia.
authors.forename: Laila N
authors.initials: LN
authors.lastname: Abudulai
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernandez
authors.forename: Karli
authors.initials: K
authors.lastname: Corscadden
authors.forename: Michael
authors.initials: M
authors.lastname: Hunter
authors.forename: Lea-Ann S
authors.initials: LA
authors.lastname: Kirkham
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Post
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000097:blood; D001402:B-Lymphocytes / Q000145:classification / Q000502:physiology*; D015536:Down-Regulation; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D022242:Pneumococcal Vaccines / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D017464:Receptors, Complement 3d / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D000907:Antibodies, Bacterial; C482586:BTLA protein, human; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D017464:Receptors, Complement 3d; D011971:Receptors, Immunologic; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human