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Associations Between B-Cell Subsets and Subclinical Coronary Artery Disease in Ugandans With and Without HIV
Laventa M Obare1, Tecla M Temu2, Tan Ding3
1Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Insights
People living with HIV have fewer naive B cells, linked to atherosclerosis. Higher naive B cell levels may protect against cardiovascular disease in HIV patients.
Area of Science:
- Immunology
- Cardiovascular Disease Research
- HIV/AIDS Research
Background:
- People living with HIV-1 (PLWH) face increased cardiovascular disease (CVD) risk due to chronic inflammation, immune dysregulation, and antiretroviral therapy (ART).
- The role of B cells in HIV-associated atherosclerosis is not well understood.
- Understanding immune cell contributions is crucial for managing CVD in PLWH.
Purpose of the Study:
- To investigate the association between B cell subsets and subclinical atherosclerosis in people living with HIV (PLWH).
- To compare immune cell profiles between PLWH and people without HIV (PWoH).
- To explore the relationship between specific immune cell populations and coronary artery disease severity.
Main Methods:
- Cross-sectional study of 40 PLWH and 60 PWoH in Uganda, matched for age and CVD risk.
- Mass cytometry used to profile peripheral blood mononuclear cells and define immune subsets.
- Coronary computed tomography angiography quantified coronary artery disease (CAD) via segment stenosis score (SSS); multivariable hurdle regression analyzed associations.
Main Results:
- PLWH had a lower proportion of CCR7- naive B cells compared to PWoH.
- Higher frequencies of CCR7- naive B cells, CXCR3+CX3CR1+ B cells, and plasmablasts were associated with lower SSS across all participants.
- HIV-positive status was independently linked to higher SSS; classical monocytes correlated with higher SSS in PLWH.
Conclusions:
- Lower frequencies of naive B cells in PLWH may be associated with subclinical atherosclerosis.
- Specific B cell subsets and monocytes show differential associations with atherosclerosis in PLWH.
- Further research is needed to elucidate the mechanisms linking B cells, immune dysregulation, and CVD in HIV.
Background:
People living with HIV-1 (PLWH) have an increased risk of cardiovascular disease (CVD), influenced by chronic inflammation, immune dysregulation, and antiretroviral therapy (ART). B cells regulate immune responses, but their contribution to HIV-associated atherosclerosis remains poorly defined.
Methods:
In a cross-sectional study, we enrolled 40 PLWH and 60 people without HIV (PWoH) in Uganda, matched 1:1.5 for age and CVD risk. Peripheral blood mononuclear cells were profiled by mass cytometry to define immune cell subsets. Coronary computed tomography angiography quantified coronary artery disease using the segment stenosis score (SSS). We used multivariable hurdle regression to estimate the effect sizes of immune clusters, atherosclerotic cardiovascular disease (ASCVD) risk score, HIV status, and gender.
Results:
Median age was 60 years, with no difference by HIV status. People living with HIV had a lower proportion of CCR7- naïve B cells than PWoH (median 1.5% vs 1.8%; P-value adjusted [padj] = .03). Across all participants, higher CCR7- naïve B cells (ratio = 0.55, P = .02), CXCR3+CX3CR1+ B cells (ratio = 0.54, P = .03), and plasmablasts (ratio = 0.57, P = .003) were associated with lower SSS. HIV-positive status was linked to nearly 3-fold higher SSS (P < .01). In stratified analyses, classical monocytes (CD14+CD16-) correlated with higher SSS among PLWH. When classical monocytes were held at the median, higher CCR7- naïve B cells were protective in PLWH (ratio = 0.55, P = .02).
Conclusions:
This exploratory study suggests that lower frequencies of naïve B cells in PLWH are associated with differences in subclinical atherosclerosis. However, the mechanisms cannot be inferred from this study.
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