Laila N Abudulai1, Sonia Fernandez, Karli Corscadden, Michael Hunter, Lea-Ann S Kirkham, Jeffrey J Post, Martyn A French. 1. *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.
Abstract
OBJECTIVES: To determine the effect of long-term antiretroviral therapy (ART) on HIV-1-induced B-cell dysfunction. DESIGN: 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.
OBJECTIVES: To determine the effect of long-term antiretroviral therapy (ART) on HIV-1-induced B-cell dysfunction. DESIGN: Comparative study of ART-naive and ART-treated HIV-infectedpatients 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: Alessandra Ruggiero; Giuseppe Rubens Pascucci; Nicola Cotugno; Sara Domínguez-Rodríguez; Stefano Rinaldi; Alfredo Tagarro; Pablo Rojo; Caroline Foster; Alasdair Bamford; Anita De Rossi; Eleni Nastouli; Nigel Klein; Elena Morrocchi; Benoit Fatou; Kinga K Smolen; Al Ozonoff; Michela Di Pastena; Katherine Luzuriaga; Hanno Steen; Carlo Giaquinto; Philip Goulder; Paolo Rossi; Ofer Levy; Savita Pahwa; Paolo Palma Journal: Front Immunol Date: 2022-03-31 Impact factor: 7.561
Authors: Laila N Abudulai; Sonia Fernandez; Karli Corscadden; Sally A Burrows; Michael Hunter; M Christian Tjiam; Lea-Ann S Kirkham; Jeffrey J Post; Martyn A French Journal: PLoS One Date: 2017-05-02 Impact factor: 3.240
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Authors: Stephanie Trend; Anderson P Jones; Lilian Cha; Scott N Byrne; Sian Geldenhuys; Marzena J Fabis-Pedrini; William M Carroll; Judith M Cole; David R Booth; Robyn M Lucas; Allan G Kermode; Martyn A French; Prue H Hart Journal: Front Immunol Date: 2018-07-13 Impact factor: 7.561