High APRIL Levels Are Associated With Slow Disease Progression and Low Immune Activation in Chronic HIV-1-Infected Patients

Liu, Yubin; Li, Xiuxia; Han, Yang; Qiu, Zhifeng; Song, Xiaojing; Li, Bingxiang; Zhang, Han; Wang, Hongye; Feng, Kai; Liu, Longding; Wang, Jingjing; Sun, Ming; Li, Taisheng

doi:10.3389/fmed.2020.00299

Cited by 6 publications

(4 citation statements)

References 50 publications

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“…Interestingly, TNFSF13, the gene encoding A proliferation-inducing ligand (APRIL), was found to be of the most protective genes in the NHP trials [28], and we found the expression levels of this gene to be increased in monocytes from HESNs when compared to the other groups. Of interest, APRIL has been associated with slower HIV disease progression in LTNP [50]. Therefore, our data suggest that natural immunity to HIV in HESNs shares some highly protective features elicited by vaccine regimens known to confer some level of protection in humans and NHP.…”

Section: Discussionmentioning

confidence: 65%

Monocyte Gene and Molecular Expression Profiles Suggest Distinct Effector and Regulatory Functions in Beninese HIV Highly Exposed Seronegative Female Commercial Sex Workers

Blondin-Ladrie

Fourcade

Modica

et al. 2022

Viruses

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We have previously reported that the female genital tract (FGT) of Beninese HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs), presented elevated frequencies of a myeloid HLA-DR+CD14+CD11c+ population presenting “tolerogenic” monocyte derived dendritic cells (MoDC) features. In order to assess whether a differential profile of monocytes may be involved in the generation of these genital MoDCs, we have herein characterized the blood monocyte compartment of Beninese HESNs (HIV-uninfected ≥ 10 years CSWs) and relevant controls (HIV-uninfected 2.5–5 years CSWs herein termed “early HESNs”), HIV-infected CSWs, and low-risk HIV-uninfected women from the general population. Transcriptomic analyses by RNA-Seq of total sorted blood monocytes demonstrate that in comparison to the control groups, HESNs present increased expression levels of FCGR2C, FCAR, ITGAX, ITGAM, CR2, CD68, and CD163 genes, associated with effector functions. Moreover, we found increased expression levels of genes associated with protection/control against SHIV/HIV such as CCL3, CCL4, CCL5, BHLHE40, and TNFSF13, as well as with immune regulation such as IL-10, Ahr, CD83, and the orphan nuclear receptor (NR)4A1, NR4A2, and NR4A3. Through multicolor flow cytometry analyses, we noticed that the frequencies of intermediate and non-classical monocyte populations tended to be elevated in the blood of HESNs, and exhibited increased expression levels of effector CD16, CD11c, CD11b, as well as regulatory HLA-G, IL-10, and IFN-α markers when compared to HIV-uninfected women and/or HIV-infected CSWs. This profile is compatible with that previously reported in the FGT of HESNs, and likely confers an enormous advantage in their resistance to HIV infection.

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Section: Discussionmentioning

confidence: 65%

Monocyte Gene and Molecular Expression Profiles Suggest Distinct Effector and Regulatory Functions in Beninese HIV Highly Exposed Seronegative Female Commercial Sex Workers

Blondin-Ladrie

Fourcade

Modica

et al. 2022

Viruses

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“…The fact that high levels of BAFF seem to correlate with low HDL and high LDL could be related to the fact that these modulations are all related to the HIV context, and thus could reflect HIV disease progression. This could also explain the positive correlation of APEIL with HDL levels and negative correlation with the LDL/HDL ratio, as APRIL has also been found to be related to a slower HIV disease progression and a lower immune activation [ 52 ]. It is important to note that the CHACS does not control for statin usage.…”

Section: Discussionmentioning

confidence: 99%

Subclinical Atherosclerosis Is Associated with Discrepancies in BAFF and APRIL Levels and Altered Breg Potential of Precursor-like Marginal Zone B-Cells in Long-Term HIV Treated Individuals

et al. 2022

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Chronic inflammation persists in people living with HIV (PLHIV) despite antiretrovial therapy (ART) and is involved in their premature development of cardiovascular diseases (CVD) such as atherosclerosis. We have previously reported that an excess of “B-cell activating factor” (BAFF), an important molecule for the selection and activation of first-line Marginal Zone (MZ) B-cell populations, is associated with deregulations of precursor-like MZ (MZp), whose potent B-cell regulatory (Breg) capacities are altered in PLHIV, early on and despite 1–2 years of ART. Based on these observations, and growing evidence that MZ populations are involved in atherosclerosis control, we designed a cross sectional study to explore the associations between BAFF and its analogue “A proliferation-inducing ligand” (APRIL) with subclinical CVD in long-time-treated individuals of the Canadian HIV and Aging Cohort Study (CHACS) imaging sub-study group. We also characterized the Breg profile of MZp from the blood of these individuals. Results were correlated with the total volume of atherosclerotic plaques (TPV) and with CVD risk factors and biomarkers. TPV was measured using cardiac computerised tomography angiography, and presence of CVD was defined as TPV > 0. We report that blood levels of BAFF are elevated and correlate positively with CVD and its risk factors in PLHIV from the CHACS, in contrast to APRIL levels, which correlate negatively with these factors. The expression levels of Breg markers such as NR4A3, CD39, CD73 and CD83 are significantly lower in PLHIV when compared to those of HIV-uninfected controls. In vitro experiments show that APRIL upregulates the expression of Breg markers by blood MZp from HIV-uninfected individuals, while this modulation is dampened by the addition of recombinant BAFF. Altogether, our observations suggest that strategies viewed to modulate levels of BAFF and/or APRIL could eventually represent a potential treatment target for CVD in PLHIV.

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“…The fact that high levels of BAFF seem to correlate with low HDL and high LDL could be related to the fact that these modulations are all related to the HIV context, and thus could reflect HIV disease progression. This could also explain APRIL’s positive correlation with HDL levels and negative correlation with the LDL/HDL ratio, as APRIL has also been found to be related to a slower HIV disease progression and a lower immune activation [50]. It is important to note that the CHACS does not control for statin usage.…”

Section: Discussionmentioning

confidence: 99%

Subclinical Atherosclerosis is Associated with Discrepancies in BAFF and APRIL Levels and Altered Breg Potential of Precursor-like Marginal Zone B-Cells in HIV Treated Individuals

Aranguren

Doyon-Laliberté

El‐Far

et al. 2022

Preprint

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Chronic inflammation persists in people living with HIV (PLHIV) despite antiretrovial therapy (ART), and is involved in their premature development of cardiovascular diseases (CVD) such as atherosclerosis. We have previously reported that an excess of "B-cell activating factor" (BAFF), an important molecule for the selection and activation of first line Marginal Zone (MZ) B-cell populations, is associated with deregulations of precursor-like MZ (MZp), whose potent B-cell regulatory (Breg) capacities are altered in PLHIV, early on and despite 1-2 years of ART. Based on these observations, and growing evidence that MZ populations are involved in atherosclerosis control, we designed a cross sectional study to explore the associations between BAFF and its analogue "A proliferation-inducing ligand" (APRIL) with subclinical CVD in long time treated individuals of the Canadian HIV and Aging Cohort Study (CHACS) imaging sub-study group. We also characterized the Breg profile of MZp from the blood of these individuals. Results were correlated with the total volume of atherosclerotic plaques (TPV) and with CVD risk factors and biomarkers. TPV was measured using cardiac computerised tomography angiography, and presence of CVD was defined as TPV > 0. We report that blood levels of BAFF are elevated and correlate positively with CVD and its risk factors in PLHIV from the CHACS, in contrast to APRIL levels, which correlate negatively with these factors. Expression levels of Breg markers such as NR4A3, CD39, CD73 and CD83 are significantly lower in PLHIV when compared to those of HIV-uninfected controls. In vitro experiments show that APRIL upregulates the expression of Breg markers by blood MZp from HIV-uninfected individuals, while this modulation is dampened by the addition of recombinant BAFF. Altogether, our observations suggest that strategies viewed to modulate levels of BAFF and/or APRIL could eventually represent a potential treatment target for CVD in PLHIV.

show abstract

High APRIL Levels Are Associated With Slow Disease Progression and Low Immune Activation in Chronic HIV-1-Infected Patients

Cited by 6 publications

References 50 publications

Monocyte Gene and Molecular Expression Profiles Suggest Distinct Effector and Regulatory Functions in Beninese HIV Highly Exposed Seronegative Female Commercial Sex Workers

Monocyte Gene and Molecular Expression Profiles Suggest Distinct Effector and Regulatory Functions in Beninese HIV Highly Exposed Seronegative Female Commercial Sex Workers

Subclinical Atherosclerosis Is Associated with Discrepancies in BAFF and APRIL Levels and Altered Breg Potential of Precursor-like Marginal Zone B-Cells in Long-Term HIV Treated Individuals

Subclinical Atherosclerosis is Associated with Discrepancies in BAFF and APRIL Levels and Altered Breg Potential of Precursor-like Marginal Zone B-Cells in HIV Treated Individuals

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