Extracellular vesicles as biomarkers for AIDS-associated non-Hodgkin lymphoma risk

Laura E Martínez; Larry I Magpantay; Yu Guo; Priya Hegde; Roger Detels; Shehnaz K Hussain; Marta Epeldegui

doi:10.3389/fimmu.2023.1259007

Extracellular vesicles as biomarkers for AIDS-associated non-Hodgkin lymphoma risk

Front Immunol. 2023 Sep 22:14:1259007. doi: 10.3389/fimmu.2023.1259007. eCollection 2023.

Authors

Laura E Martínez^{1

2}, Larry I Magpantay^{1

2}, Yu Guo^{1

2}, Priya Hegde¹, Roger Detels³, Shehnaz K Hussain⁴, Marta Epeldegui^{1

2

5}

Affiliations

¹ UCLA AIDS Institute and David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
² Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
³ Jonathan and Karin Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, United States.
⁴ Department of Public Health Sciences, School of Medicine and Comprehensive Cancer Center, University of California, Davis, Davis, CA, United States.
⁵ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

Introduction: Extracellular vesicles are membrane-bound structures secreted into the extracellular milieu by cells and can carry bioactive molecules. There is emerging evidence suggesting that EVs play a role in the diagnosis, treatment, and prognosis of certain cancers. In this study, we investigate the association of EVs bearing PD-L1 and molecules important in B-cell activation and differentiation with AIDS-NHL risk.

Methods: EVs were isolated from archived serum collected prior to the diagnosis of AIDS-NHL in cases (N = 51) and matched HIV+ controls (N = 52) who were men enrolled in the Los Angeles site of the MACS/WIHS Combined Cohort Study (MWCCS). Serum specimens of AIDS-NHL cases were collected at a mean time of 1.25 years (range of 2 to 36 months) prior to an AIDS-NHL diagnosis. The expression of PD-L1 and other molecules on EVs (CD40, CD40L, TNF-RII, IL-6Rα, B7-H3, ICAM-1, and FasL) were quantified by Luminex multiplex assay.

Results and discussion: We observed significantly higher levels of EVs bearing PD-L1, CD40, TNF-RII and/or IL-6Rα in AIDS-NHL cases compared with controls. Using multivariate conditional logistic regression models adjusted for age and CD4⁺ T-cell count, we found that EVs bearing PD-L1 (OR = 1.93; 95% CI: 1.10 - 3.38), CD40 (OR = 1.97, 95% CI: 1.09 - 3.58), TNF-RII (OR = 5.06; 95% CI: 1.99 - 12.85) and/or IL-6Rα (OR = 4.67; 95% CI: 1.40 - 15.53) were significantly and positively associated with AIDS-NHL risk. In addition, EVs bearing these molecules were significantly and positively associated with non-CNS lymphoma: PD-L1 (OR = 1.94; 95% CI: 1.01 - 3.72); CD40 (OR = 2.66; 95% CI: 1.12 - 6.35); TNF-RII (OR = 9.64; 95% CI: 2.52 - 36.86); IL-6Rα (OR = 8.34; 95% CI: 1.73 - 40.15). These findings suggest that EVs bearing PD-L1, CD40, TNF-RII and/or IL-6Rα could serve as biomarkers for the early detection of NHL in PLWH.

Keywords: AIDS-NHL; CD40; IL-6Rα; PD-L1; TNF-RII; biomarkers; extracellular vesicles.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Acquired Immunodeficiency Syndrome* / complications
B7-H1 Antigen / metabolism
Biomarkers
Cohort Studies
Extracellular Vesicles* / metabolism
Female
Humans
Lymphoma, Non-Hodgkin* / complications
Lymphoma, Non-Hodgkin* / diagnosis
Male
Receptors, Tumor Necrosis Factor, Type II

Substances

B7-H1 Antigen
Receptors, Tumor Necrosis Factor, Type II
Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding