Open AccessLeukocyte and cytokine variables in asymptomatic Pugs at genetic risk of necrotizing meningoencephalitis
Author(s) -
Windsor Rebecca,
Stewart Samuel D.,
Talboom Joshua,
Lewis Candace,
Naymik Marcus,
Piras Ignazio S.,
Keller Stefan,
Borjesson Dori L.,
Clark Gary,
Khanna Chand,
Huentelman Matthew
Publication year - 2021
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/jvim.16293
Subject(s) - medicine , asymptomatic , haplotype , gastroenterology , immunology , meningoencephalitis , genotype , genetics , biology , gene
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 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 Forty Pug dogs asymptomatic for NME from a hospital sample. 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 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 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.