Published online Nov 12, 2016. doi: 10.5501/wjv.v5.i4.155
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
To evaluate alterations of memory B cell subpopulations during a 48-wk period in human immunodeficiency virus type 1 (HIV-1) patients.
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.
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.
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.
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.