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J Infect Dis. 2019 Aug 23. pii: jiz423. doi: 10.1093/infdis/jiz423. [Epub ahead of print]

Plasma levels of C-type lectin REG3α and gut damage in people with HIV.

Author information

1
Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montreal, QC, Canada.
2
Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.
3
Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
4
Department of Laboratory Medicine, University Medical Center, University of Groningen, The Netherlands.
5
Department of Biological Sciences, University of Quebec at Montreal (UQAM), Montreal, Quebec, Canada.
6
Centre de recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
7
Département de microbiologie, infectiologie et immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada.
8
Department of Medicine, McGill University, Montreal, QC, Canada.
9
Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
10
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
11
Division of gastroenterology and hepatology, McGill University Health Centre, QC, Canada.
12
Division of Hematology, McGill University Health Centre, Montreal, QC, Canada.

Abstract

BACKGROUND:

Regenerating islet-derived protein-3α (REG3α) is an antimicrobial peptide secreted by intestinal Paneth cells. Circulating REG3α has been identified as a gut damage marker in inflammatory bowel diseases. People with HIV (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation and development of non-AIDS co-morbidities. Herein, we assessed REG3α as a marker of gut damage in PWH.

METHODS:

Plasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 HIV-uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation and immune activation markers.

RESULTS:

Cross-sectionally, REG3α levels were elevated in untreated and ART-treated PWH compared with controls. ECs also had elevated REG3α levels compared to controls. Longitudinally, REG3α levels increased in PWH without ART and decreased in those who initiated ART. REG3α levels were inversely associated with CD4 T-cell count and CD4/CD8 ratio, while positively correlated with HIV viral load in untreated participants, and with fungal products translocation and inflammatory markers in all PWH.

CONCLUSION:

Plasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3 may be used to evaluate therapeutic interventions and predict non-AIDS co-morbidities risks in PWH.

KEYWORDS:

HIV; REG3α; gut damage; inflammation; microbial translocation

PMID:
31504638
DOI:
10.1093/infdis/jiz423

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