Transcriptome and proteome analysis of dogs with precursor targeted immune-mediated anemia treated with splenectomy

PLoS One. 2023 May 5;18(5):e0285415. doi: 10.1371/journal.pone.0285415. eCollection 2023.

Abstract

Precursor-targeted immune-mediated anemia (PIMA) in dogs is characterized by persistent non-regenerative anemia and ineffective erythropoiesis, and it is suspected to be an immune-mediated disease. Most affected dogs respond to immunosuppressive therapies; however, some are resistant. In this study, we carried out splenectomy as an alternative therapy for refractory PIMA in dogs, and analyzed gene expression levels in the spleen of dogs with or without PIMA and in serum before and after splenectomy. A total of 1,385 genes were found to express differentially in the spleens from dogs with PIMA compared with healthy dogs by transcriptome analysis, of which 707 genes were up-regulated, including S100A12, S100A8, and S100A9 that are linked directly to the innate immune system and have been characterized as endogenous damage-associated molecular patterns. Furthermore, immunohistochemistry confirmed that S100A8/A9 protein expression levels were significantly higher in dogs with PIMA compared with those in healthy dogs. A total of 22 proteins were found to express differentially between the serum samples collected before and after splenectomy by proteome analysis, of which 12 proteins were up-regulated in the samples before. The lectin pathway of complement activation was identified by pathway analysis in pre-splenectomy samples. We speculated that S100A8/9 expression may be increased in the spleen of dogs with PIMA, resulting in activation of the lectin pathway before splenectomy. These findings further our understanding of the pathology and mechanisms of splenectomy for PIMA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia* / genetics
  • Anemia* / veterinary
  • Animals
  • Calgranulin A
  • Calgranulin B
  • Dogs
  • Potassium Iodide
  • Proteome*
  • Splenectomy
  • Transcriptome

Substances

  • Proteome
  • Potassium Iodide
  • Calgranulin A
  • Calgranulin B

Grants and funding

This study was supported by the Japan Society for the Promotion of Science, KAKENHI (https://www.jsps.go.jp/english/index.html) and Japan Science and Technology Agency Support for Pioneering Research Initiated by the Next Generation (https://www.jst.go.jp/jisedai/en/index.html)[grant number 19K15991 and JPMJSP2119]. KM received 19K15991 and MS received JPMJSP2119. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.