Leukocyte and cytokine variables in asymptomatic Pugs at genetic risk of necrotizing meningoencephalitis.
cytokine
genetic risk
immune dysregulation
necrotizing meningoencephalitis
Journal
Journal of veterinary internal medicine
ISSN: 1939-1676
Titre abrégé: J Vet Intern Med
Pays: United States
ID NLM: 8708660
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
revised:
10
10
2021
received:
25
03
2021
accepted:
13
10
2021
pubmed:
24
10
2021
medline:
24
12
2021
entrez:
23
10
2021
Statut:
ppublish
Résumé
Necrotizing meningoencephalitis (NME, aka Pug dog encephalitis) is an inflammatory brain condition associated with advanced disease at initial presentation, rapid progression, and poor response to conventional immunomodulatory therapy. That genetic risk for NME, defined by a common germline DNA haplotype located on chromosome 12, is associated with altered blood cytokine concentrations and leukocyte subsets in asymptomatic Pugs. Forty Pug dogs asymptomatic for NME from a hospital sample. Prospective observational cohort study, including germline genome-wide genotyping, plasma cytokine determination by multiplexed profiling, and leukocyte subset characterization by flow cytometric analysis. Seven (18%) dogs were high risk, 10 (25%) medium risk, and 23 (58%) low risk for NME, giving a risk haplotype frequency of 30%. High and medium risk Pugs had significantly lower proportion of CD4+ T cells (median 22% [range, 7.3%-38%] vs 29% [range, 16%-41%], P = .03) and higher plasma IL-10 concentrations than low-risk Pugs (median 14.11 pg/mL [range, 9.66-344.19 pg/mL] vs 12.21 pg/mL [range, 2.59-18.53 pg/mL], P = .001). No other variables were significantly associated with the NME haplotype-based risk. These data suggest an immunological underpinning to NME and a biologic rationale for future clinical trials that investigate novel diagnostic, preventative, and therapeutic strategies for this disease.
Sections du résumé
BACKGROUND
BACKGROUND
Necrotizing meningoencephalitis (NME, aka Pug dog encephalitis) is an inflammatory brain condition associated with advanced disease at initial presentation, rapid progression, and poor response to conventional immunomodulatory therapy.
HYPOTHESIS/OBJECTIVES
OBJECTIVE
That genetic risk for NME, defined by a common germline DNA haplotype located on chromosome 12, is associated with altered blood cytokine concentrations and leukocyte subsets in asymptomatic Pugs.
ANIMALS
METHODS
Forty Pug dogs asymptomatic for NME from a hospital sample.
METHODS
METHODS
Prospective observational cohort study, including germline genome-wide genotyping, plasma cytokine determination by multiplexed profiling, and leukocyte subset characterization by flow cytometric analysis.
RESULTS
RESULTS
Seven (18%) dogs were high risk, 10 (25%) medium risk, and 23 (58%) low risk for NME, giving a risk haplotype frequency of 30%. High and medium risk Pugs had significantly lower proportion of CD4+ T cells (median 22% [range, 7.3%-38%] vs 29% [range, 16%-41%], P = .03) and higher plasma IL-10 concentrations than low-risk Pugs (median 14.11 pg/mL [range, 9.66-344.19 pg/mL] vs 12.21 pg/mL [range, 2.59-18.53 pg/mL], P = .001). No other variables were significantly associated with the NME haplotype-based risk.
CONCLUSIONS AND CLINICAL IMPORTANCE
CONCLUSIONS
These data suggest an immunological underpinning to NME and a biologic rationale for future clinical trials that investigate novel diagnostic, preventative, and therapeutic strategies for this disease.
Identifiants
pubmed: 34687084
doi: 10.1111/jvim.16293
pmc: PMC8692191
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Observational Study, Veterinary
Langues
eng
Sous-ensembles de citation
IM
Pagination
2846-2852Informations de copyright
© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Références
Cell. 2017 Mar 23;169(1):72-84.e13
pubmed: 28340352
J Vet Intern Med. 2014 Jan-Feb;28(1):198-203
pubmed: 24428322
Am J Hum Genet. 2007 Nov;81(5):1084-97
pubmed: 17924348
Tissue Antigens. 2010 Aug;76(2):110-8
pubmed: 20403140
J Vet Intern Med. 2021 Nov;35(6):2846-2852
pubmed: 34687084
Science. 2002 Jun 21;296(5576):2225-9
pubmed: 12029063
J Hered. 2011 Sep-Oct;102 Suppl 1:S40-6
pubmed: 21846746
PLoS One. 2014 Nov 13;9(11):e112755
pubmed: 25393235
Front Immunol. 2020 Jun 26;11:1315
pubmed: 32670290
Res Vet Sci. 2009 Jun;86(3):438-42
pubmed: 19014875
Transplantation. 1999 May 27;67(10):1329-35
pubmed: 10360586
Vet Pathol. 2013 Nov;50(6):1127-34
pubmed: 23651736
Tissue Antigens. 1992 Aug;40(2):75-85
pubmed: 1412420
Sci Rep. 2017 Apr 26;7(1):1207
pubmed: 28446795
Nat Genet. 2009 Jul;41(7):824-8
pubmed: 19525955
Am J Pathol. 1996 May;148(5):1699-708
pubmed: 8623937
J Vet Intern Med. 2008 Jul-Aug;22(4):961-8
pubmed: 18647157
Vet Pathol. 2008 May;45(3):336-46
pubmed: 18487490
Bioinformatics. 2005 Jan 15;21(2):263-5
pubmed: 15297300
Nat Rev Immunol. 2017 Jan;17(1):49-59
pubmed: 27916979
Vet Pathol. 1989 May;26(3):191-4
pubmed: 2763409