Chronic HIV-1 Infection Induces B-Cell Dysfunction That Is Incompletely Resolved by Long-Term Antiretroviral Therapy.

Autor: Abudulai LN; 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., Fernandez S, Corscadden K, Hunter M, Kirkham LA, Post JJ, French MA
Jazyk: angličtina
Zdroj: Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2016 Apr 01; Vol. 71 (4), pp. 381-9.
DOI: 10.1097/QAI.0000000000000869
Abstrakt: 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.
Databáze: MEDLINE