Cytokine expression in subjects with Mycobacterium avium ssp. paratuberculosis positive blood cultures and a meta-analysis of cytokine expression in Crohn's disease

J. Todd Kuenstner, Qiang Xu*, Tim J. Bull, Antonio Foddai, Irene R. Grant, Saleh Naser, Raghava Potula, Peilin Zhang, Ira Shafran, Serhat Emre Akhanli, Svetlana Khaiboullina, Russell Kruzelock

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Objectives: 1) Culture Mycobacterium avium ssp. paratuberculosis (MAP) from blood, 2) assess infection persistence, 3) determine CD cytokine expression, 3) compare CD cytokine expression to tuberculosis, and 4) perform a meta-analysis of cytokine expression in CD.
Methods: The Temple University/Abilene Christian University (TU/ACU) study had a prospective case control design with 201 subjects including 61 CD patients and 140 non-CD controls. The culture methods included the MGIT, TiKa and Pozzato, and were deemed MAP positive, if IS900 PCR positive. A phage amplification assay was also performed to detect MAP. Cytokine analysis of the TU/ACU samples was performed using Simple Plex cytokine reagents on the Ella ELISA system. Statistical analyses were done after log transformation using the R
software package. The meta-analysis combined three studies.
Results: Most subjects had MAP positive blood cultures by one or more methods in 3 laboratories. In our cytokine study comparing CD to non-CD controls, IL-17, IFNγ and TNFα were significantly increased in CD, but IL-2, IL-5, IL-10 and GM-CSF were not increased. In the meta-analysis, IL-6, IL-8 and IL-12 were significantly increased in the CD patients.
Conclusions: Most subjects in our sample had MAP infection and 8 of 9 subjects remained MAP positive one year later indicating persistent infection. While not identical, cytokine expression patterns in MAP culture positive CD patients in the TU/ACU study showed similarities (increased IL-17, IFNγ and TNFα) to patterns of patients with TB in other studies, indicating the possibilities of similar mechanisms of pathogen infection and potential strategies for treatment.
Original languageEnglish
JournalFrontiers in Cellular and Infection Microbiology
Publication statusPublished - 13 Feb 2024

Keywords

  • Mycobacterium avium subsp. paratuberculosis
  • autoimmune disease
  • Crohn’s Disease
  • bacteremia
  • Inflammatory bowel disease (IBD)

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