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

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.

Automated summary

In this study, splenectomy was performed as an alternative therapy for refractory PIMA in dogs, and gene expression levels in the spleens and serum of dogs with PIMA were analyzed. Transcriptome analysis revealed differential gene expression in the spleens of dogs with PIMA, with up-regulation of genes such as S100A12, S100A8, and S100A9. Immunohistochemistry confirmed higher levels of S100A8/A9 protein expression in dogs with PIMA. Proteome analysis identified differentially expressed proteins in the serum samples before and after splenectomy, with up-regulation of proteins in the pre-splenectomy samples. Pathway analysis revealed the involvement of the lectin pathway of complement activation in the pre-splenectomy samples. These findings provide deeper insights into the pathology and mechanisms of splenectomy for PIMA.