Randomised controlled trial of fractionated and unfractionated prednisolone regimens for dogs with immune-mediated haemolytic anaemia.

METHODS: A randomised non-blinded non-inferiority trial was conducted to determine whether treatment with an unfractionated regimen of oral prednisolone was inferior to a fractionated regimen for dogs with primary immune-mediated haemolytic anaemia. Dogs received the same total daily dose of prednisolone as unfractionated (group 1, starting at 4 mg/kg orally once daily) or fractionated (group 2, starting at 2 mg/kg orally twice daily) doses. Questionnaires were administered to owners to assess adverse effects and quality of life (QoL). End points included survival to eight weeks, and changes in QoL and clinicopathological parameters over time. RESULTS: Thirty-nine dogs were enrolled in the study, of which 5 were withdrawn and 17 were assigned to each group. The number of cases recruited was insufficient to determine whether unfractionated treatment was inferior to fractionated. Total serum bilirubin decreased more rapidly in dogs in group 2, whereas polydipsia improved more rapidly in group 1. Blood pressure and score for polyuria were higher in dogs in group 2 over time, whereas lymphocyte concentration was lower. CONCLUSION: Administration of the same total daily dose of prednisolone as an unfractionated dose resulted in fewer adverse effects but the effect on survival could not be assessed in this study.

Analysis of DLA-DQB1 and polymorphisms in CTLA4 in Cocker spaniels affected with immune-mediated haemolytic anaemia.

BACKGROUND: Cocker spaniels are predisposed to immune-mediated haemolytic anaemia (IMHA), suggesting that genetic factors influence disease susceptibility. Dog leukocyte antigen (DLA) class II genes encode major histocompatibility complex (MHC) molecules that are involved in antigen presentation to CD4(+) T cells. Several DLA haplotypes have been associated with autoimmune disease, including IMHA, in dogs, and breed specific differences have been identified. Cytotoxic T lymphocyte antigen 4 (CTLA4) is a critical molecule involved in the regulation of T-cell responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 promoter have been shown to be associated with several autoimmune diseases in humans and more recently with diabetes mellitus and hypoadrenocorticism in dogs. The aim of the present study was to investigate whether DLA-DQB1 alleles or CTLA4 promoter variability are associated with risk of IMHA in Cocker spaniels. RESULTS: There were a restricted number of DLA-DQB1 alleles identified, with a high prevalence of DLA-DQB1*007:01 in both groups. A high prevalence of DLA-DQB1 homozygosity was identified, although there was no significant difference between IMHA cases and controls. CTLA4 promoter haplotype diversity was limited in Cocker spaniels, with all dogs expressing at least one copy of haplotype 8. There was no significant difference comparing haplotypes in the IMHA affected group versus control group (p = 0.23). Homozygosity for haplotype 8 was common in Cocker spaniels with IMHA (27/29; 93 %) and in controls (52/63; 83 %), with no statistically significant difference in prevalence between the two groups (p = 0.22). CONCLUSIONS: DLA-DQB1 allele and CTLA4 promoter haplotype were not found to be significantly associated with IMHA in Cocker spaniels. Homozygosity for DLA-DQB1*007:01 and the presence of CTLA4 haplotype 8 in Cocker spaniels might increase overall susceptibility to IMHA in this breed, with other genetic and environmental factors involved in disease expression and progression.