Investigation of the therapeutic effects, predictors, and complications of long-term immunosuppressive therapy in dogs with precursor-targeted immune-mediated anemia.

Dogs with precursor-targeted immune-mediated anemia (PIMA) are commonly treated with immunosuppressive therapy, but information on predictors of treatment response and response time is limited. Therefore, we retrospectively investigated predictive factors that influenced the treatment response and duration required to observe a response in dogs with PIMA receiving continuous immunosuppressive therapies for more than 105 days. Of 50 client-owned dogs that developed PIMA, 27 were included in this study, of which 18 were responders and 9 were non-responders to immunosuppressive therapies. Sixteen of the 18 responders responded to treatment within 60 days and the remaining 2 responded at 93 and 126 days, respectively. We found that an erythroid-maturation ratio of <0.17 may be a useful predictor for treatment response. In addition, complications of immunosuppressive therapies were investigated further in 50 dogs. Pancreatitis (n=4) and pneumonia (3) occurred over the entire treatment period, and infections such as abscesses (3) tended to be more common in dogs on an extended period of immunosuppressive therapy. These findings may be helpful when planning for the initial treatment and may provide evidence for informed consent about potential comorbidities throughout the treatment course.

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.