Plasma Levels of C-Type Lectin REG3α and Gut Damage in People With Human Immunodeficiency Virus.
Adult
Anti-HIV Agents
/ therapeutic use
Bacterial Translocation
Biomarkers
/ blood
CD4-CD8 Ratio
Cross-Sectional Studies
Disease Progression
Fatty Acid-Binding Proteins
/ blood
Female
HIV Infections
/ blood
HIV-1
Humans
Interleukin-6
/ blood
Interleukin-8
/ blood
Interleukins
/ blood
Intestinal Mucosa
/ pathology
Lipopolysaccharide Receptors
/ blood
Lipopolysaccharides
/ blood
Male
Middle Aged
Pancreatitis-Associated Proteins
/ blood
Tumor Necrosis Factor-alpha
/ blood
Viral Load
beta-Glucans
/ blood
Interleukin-22
HIV
REG3α
gut damage
inflammation
microbial translocation
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
01 01 2020
01 01 2020
Historique:
received:
06
06
2019
accepted:
14
08
2019
pubmed:
11
9
2019
medline:
4
8
2020
entrez:
11
9
2019
Statut:
ppublish
Résumé
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 living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH. Plasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 human immunodeficiency virus (HIV)-uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation, and immune activation markers. 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 product translocation and inflammatory markers in all PWH. Plasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH.
Sections du résumé
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 living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. 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 human immunodeficiency virus (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 product translocation and inflammatory markers in all PWH.
CONCLUSIONS
Plasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH.
Identifiants
pubmed: 31504638
pii: 5553837
doi: 10.1093/infdis/jiz423
pmc: PMC6910878
doi:
Substances chimiques
Anti-HIV Agents
0
Biomarkers
0
CD14 protein, human
0
CXCL8 protein, human
0
FABP2 protein, human
0
Fatty Acid-Binding Proteins
0
IL6 protein, human
0
Interleukin-6
0
Interleukin-8
0
Interleukins
0
Lipopolysaccharide Receptors
0
Lipopolysaccharides
0
Pancreatitis-Associated Proteins
0
REG3A protein, human
0
Tumor Necrosis Factor-alpha
0
beta-Glucans
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110-121Subventions
Organisme : CIHR
ID : MOP 103230
Pays : Canada
Organisme : CIHR
ID : 154051
Pays : Canada
Organisme : CIHR
ID : PJT 166049
Pays : Canada
Organisme : CIHR
ID : HIG133050
Pays : Canada
Organisme : CIHR
ID : HB2-164064
Pays : Canada
Organisme : CIHR
ID : MOP93770
Pays : Canada
Organisme : CIHR
ID : TCO-125276
Pays : Canada
Organisme : CIHR
ID : HAL-157985
Pays : Canada
Investigateurs
C Milne
(C)
S Lavoie
(S)
J Friedman
(J)
M Duchastel
(M)
F Villielm
(F)
F Asselin
(F)
M Boissonnault
(M)
P J Maziade
(PJ)
S Lavoie
(S)
M Milne
(M)
N Z Miaki
(NZ)
M E Thériault
(ME)
B Lessard
(B)
M A Charron
(MA)
S Dufresne
(S)
M E Turgeon
(ME)
S Vézina
(S)
E Huchet
(E)
J P Kerba
(JP)
M Poliquin
(M)
S Poulin
(S)
P Rochette
(P)
P Junod
(P)
D Longpré
(D)
R Pilarski
(R)
E Sasseville
(E)
L Charest
(L)
A Hamel
(A)
A Cloutier-Blais
(A)
S Massoud
(S)
F Chano
(F)
B Trottier
(B)
L Labrecque
(L)
C Fortin
(C)
V Hal-Gagne
(V)
M Munoz
(M)
B Deligne
(B)
V Martel-Laferrière
(V)
B Trottier
(B)
M E Goyer
(ME)
M Teltscher
(M)
A de Pokomandy
(A)
J Cox
(J)
E Beauchamp
(E)
M Klein
(M)
L P Haraoui
(LP)
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Références
Nat Med. 2006 Dec;12(12):1365-71
pubmed: 17115046
PLoS One. 2014 May 12;9(5):e97171
pubmed: 24819230
Am J Epidemiol. 2010 Aug 15;172(4):363-71
pubmed: 20660122
PLoS Pathog. 2010 Aug 19;6(8):e1001052
pubmed: 20808901
Endocrinology. 2019 Jun 1;160(6):1506-1514
pubmed: 31070724
Mucosal Immunol. 2012 Nov;5(6):670-80
pubmed: 22854709
J Clin Invest. 2018 Nov 1;128(11):4970-4979
pubmed: 30106382
J Infect Dis. 2014 Oct 15;210(8):1248-59
pubmed: 24795473
AIDS. 2016 Jun 19;30(10):1617-27
pubmed: 27045377
Aliment Pharmacol Ther. 2014 Oct;40(8):974-81
pubmed: 25112824
Front Immunol. 2019 Mar 18;10:465
pubmed: 30967860
PLoS Pathog. 2017 Feb 27;13(2):e1006202
pubmed: 28241080
Clin Infect Dis. 2019 Apr 8;68(8):1394-1401
pubmed: 30137242
Scand J Clin Lab Invest. 2008;68(8):767-70
pubmed: 18622801
Sci Transl Med. 2016 Sep 28;8(358):358ra125
pubmed: 27683550
EBioMedicine. 2016 Jan 26;4:40-9
pubmed: 26981570
Sci Transl Med. 2013 Jul 10;5(193):193ra91
pubmed: 23843452
J Infect Dis. 2015 Jun 1;211(11):1692-702
pubmed: 25512624
Blood. 2007 Apr 1;109(7):2912-20
pubmed: 17164338
J Virol. 2014 Apr;88(8):4533-42
pubmed: 24501416
JAMA. 2006 Sep 27;296(12):1498-506
pubmed: 17003398
Blood. 2011 Dec 15;118(25):6702-8
pubmed: 21979939
J Infect Dis. 2015 Aug 1;212(3):355-66
pubmed: 25616404
J Clin Pathol. 1989 Mar;42(3):275-81
pubmed: 2703544
Gastroenterol Res Pract. 2017;2017:1745918
pubmed: 29201046
Gastroenterology. 2018 Mar;154(4):1009-1023.e14
pubmed: 29133078
Open Forum Infect Dis. 2015 Jan 13;2(1):ofu117
pubmed: 25884005
J Int AIDS Soc. 2018 Feb;21(2):
pubmed: 29412520
Viruses. 2018 Apr 26;10(5):
pubmed: 29701691
Mucosal Immunol. 2010 Jul;3(4):387-98
pubmed: 20357762
AIDS. 2007 Feb 19;21(4):433-9
pubmed: 17301561
Aliment Pharmacol Ther. 2013 Feb;37(4):482-90
pubmed: 23289539
J Virus Erad. 2017 Oct 1;3(4):212-217
pubmed: 29057085
Clin Infect Dis. 2018 Nov 12;:
pubmed: 30418519
Inflamm Bowel Dis. 2003 May;9(3):162-70
pubmed: 12792221
BMC Infect Dis. 2017 Sep 11;17(1):611
pubmed: 28893184
Clin Infect Dis. 2017 Jan 15;64(2):124-131
pubmed: 27737952
Nat Rev Microbiol. 2011 May;9(5):356-68
pubmed: 21423246
Mucosal Immunol. 2018 Sep;11(5):1429-1440
pubmed: 29907866
Drugs. 2016 Apr;76(5):533-49
pubmed: 26915027
Front Immunol. 2019 Feb 21;10:289
pubmed: 30846990
Open Forum Infect Dis. 2018 Nov 05;5(11):ofy288
pubmed: 30515430
Clin Infect Dis. 2019 Mar 16;:null
pubmed: 30877304
Nature. 2014 Jan 2;505(7481):103-7
pubmed: 24256734
J Acquir Immune Defic Syndr. 2019 Feb 1;80(2):242-245
pubmed: 30422903
Gastroenterology. 1991 Jun;100(6):1521-7
pubmed: 2019358