Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virol. Nov 12, 2016; 5(4): 155-160
Published online Nov 12, 2016. doi: 10.5501/wjv.v5.i4.155
Antiretroviral naive and treated patients: Discrepancies of B cell subsets during the natural course of human immunodeficiency virus type 1 infection
Olga Tsachouridou, Lemonia Skoura, Pantelis Zebekakis, Apostolia Margariti, Adamantini Georgiou, Dimitrios Bougiouklis, Dimitrios Pilalas, Antonios Galanos, Michael Daniilidis, Symeon Metallidis
Olga Tsachouridou, Lemonia Skoura, Pantelis Zebekakis, Adamantini Georgiou, Dimitrios Pilalas, Antonios Galanos, Michael Daniilidis, Symeon Metallidis, 1st Internal Medicine Department, Infectious Diseases Division, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Apostolia Margariti, Dimitrios Bougiouklis, National AIDS Reference Centre of Northern Greece, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Author contributions: Tsachouridou O participated in recruiting patients, designing the study and in the writing of the manuscript; Skoura L, Zebekakis P and Daniilidis M contributed equally to this work and have designed, organized the study and edited the text and approved the final version of the manuscript; Margariti A, Bougiouklis D and Pilalas D contributed equally to this work and have processed the samples and executed the flow cytometry and extracted/interpreted the results and wrote part of the manuscript; Georgiou A and Galanos A contributed equally to this work and have performed the statistical analysis of the study, wrote part of the manuscipt and approved the final version of the article; Metallidis S participated in recruiting patients and drafting, writing and revised on the content of the manuscript; all authors have read and approved the final version of the article to be published.
Institutional review board statement: All blood samples from the patients were taken after informed consent and ethical permission was obtained for participation in the study.
Institutional animal care and use committee statement: No animal subjects were used in this study.
Conflict-of-interest statement: There are no conflicts of interest.
Data sharing statement: No additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Olga Tsachouridou, MD, PhD, Research Associate of Infectious Diseases Unit, 1st Internal Medicine Department, Infectious Diseases Division, Medical School, Aristotle University of Thessaloniki, 1 Stilponos Kyriakidi Street, 54636 Thessaloniki, Greece. olgat_med@hotmail.com
Telephone: +30-2310-994656 Fax: +30-2310-993272
Received: April 22, 2016
Peer-review started: April 23, 2016
First decision: June 6, 2016
Revised: July 25, 2016
Accepted: August 17, 2016
Article in press: August 18, 2016
Published online: November 12, 2016
Abstract
AIM

To evaluate alterations of memory B cell subpopulations during a 48-wk period in human immunodeficiency virus type 1 (HIV-1) patients.

METHODS

Forty-one antiretroviral naïve and 41 treated HIV-1 patients matched for age and duration of HIV infection were recruited. All clinical, epidemiological and laboratory data were recorded or measured. The different B cell subsets were characterized according to their surface markers: Total B cells (CD19+), memory B cells (CD19+CD27+, BMCs), resting BMCs (CD19+CD27+CD21high, RM), exhausted BMCs (CD19+CD21lowCD27-, EM), IgM memory B (CD19+CD27+IgMhigh), isotype-switched BMCs (CD19+CD27+IgM-, ITS) and activated BMCs (CD19+CD21low+CD27+, AM) at baseline on week 4 and week 48.

RESULTS

Mean counts of BMCs were higher in treated patients. There was a marginal upward trend of IgM memory B cell proportions which differed significantly in the treated group (overall trend, P = 0.004). ITS BMC increased over time significantly in all patients. Naive patients had of lower levels of EM B cells compared to treated, with a downward trend, irrespectively of highly active antiretroviral therapy (HAART) intake. Severe impairment of EM B cells was recorded to both treated (P = 0.024) and naive (P = 0.023) and patients. Higher proportions of RM cells were noted in HAART group, which differed significantly on week 4th (P = 0.017) and 48th (P = 0.03). Higher levels of AM were preserved in HAART naive group during the whole study period (week 4: P = 0.018 and 48: P = 0.035). HIV-RNA viremia strongly correlated with AM B cells (r = 0.54, P = 0.01) and moderately with RM cells (r = -0.45, P = 0.026) at baseline.

CONCLUSION

HIV disrupts memory B cell subpopulations leading to impaired immunologic memory over time. BMC, RM, EM and ITS BMC were higher in patients under HAART. Activated BMCs (AM) were higher in patients without HAART. Viremia correlated with AM and RM. Significant depletion was recorded in EM B cells irrespectively of HAART intake. Perturbations in BMC-populations are not fully restored by antiretrovirals.

Keywords: B cell subpopulations, Time-trend, Memory cells, Human immunodeficiency virus infection, Highly active antiretroviral therapy

Core tip: During the progress of human immunodeficiency virus (HIV) infection and viral replication functional irritations of memory B-cell (BMC) compartment occur. Depletion of BMCs is one hallmark of deregulation in HIV-1 infection. Diminished levels of IgM+ BMCs are also noted. Additionally, resting BMCs are severely impaired and defective B-cell subsets, like exhausted and activated BMCs circulate in peripheral blood. Significant fluctuations of these B cells’ frequencies are recorded over time and antiretroviral therapy may play a role on this observation. Assessing these populations could potentially lead to improvement in assessing vaccine responses and tracing vulnerable patients to certain infections.