Lymphocyte immunophenotype in dogs with immune-mediated hematologic disease.

Abstract

Immune-mediated hematologic diseases (IMHD) including immune-mediated hemolytic anemia (IMHA) and immune thrombocytopenia (ITP) can cause severe disease in dogs. The underlying immune system abnormalities associated with these conditions is not known. The hypotheses of this study were that dogs with IMHD would have increased frequencies of CD4+ and CD8 + lymphocytes, decreased frequencies and numbers of T regulatory cells, and increased frequencies of interleukin (IL)-17 + lymphocytes. Fifteen dogs with newly diagnosed IMHA or ITP and 15 healthy control dogs were recruited for this prospective study. Flow cytometry was used to enumerate CD4 + lymphocytes, CD8 + lymphocytes, T regulatory (CD4 + CD25 + Foxp3+) cells, and lymphocytes secreting IL-17 in dogs with IMHD at diagnosis, then 2 and 4 days after starting immunosuppressive treatment. Median proportion of CD4+ (Day 0: 3.4%, Day 2: 3.3%) and CD8+ (Day 0: 1%, Day 2: 0.6%) cells was lower in dogs with IMHD compared to control dogs (CD4 + 22.8%, CD8 + : 13.6%; P < 0.0001 for each). Additionally, T regulatory cells were reduced in IMHD dogs at Day 0 (0.2% versus 0.6% of total lymphocytes, P = 0.0025). Dogs with IMHD had a higher proportion of lymphocytes positive for IL-17 at Day 2 (1.3%) compared to control dogs (0.4%, P = 0.0024). Dogs with IMHD have immune system alterations at diagnosis and during early treatment characterized by a deficiency in T regulatory cells and an increase in IL-17 + lymphocyte. These changes might contribute to the pathogenesis of IMHA and ITP.