Leukocyte and cytokine variables in asymptomatic Pugs at genetic risk of necrotizing meningoencephalitis

Rebecca Windsor, Samuel D. Stewart, Joshua Talboom, Candace Lewis, Marcus Naymik, Ignazio S. Piras, Stefan Keller, Dori L. Borjesson, Gary Clark, Chand Khanna, Matthew Huentelman

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
JournalJournal of Veterinary Internal Medicine
StateAccepted/In press - 2021


  • cytokine
  • genetic risk
  • immune dysregulation
  • necrotizing meningoencephalitis

ASJC Scopus subject areas

  • veterinary(all)


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