Dynamic changes in clinicopathological variables and gene expression in dogs with immune-mediated hemolytic anemia
James W. Swann, Sivert Nerhagen, Balazs Szladovits, Gina Parkes, Anna Riddle, Samantha Mason, Brian Catchpole, Yu-Mei Chang, Barbara GlanemannBackground
Immune-mediated hemolytic anemia (IMHA) is a common autoimmune disease of dogs that is difficult to treat effectively. Little is known about how clinicopathological and immune variables change with time in dogs with IMHA, and whether these changes could guide therapeutic interventions.
Aims
To investigate dynamic changes in clinicopathological variables as well as immune and glucocorticoid-regulated gene expression in dogs with IMHA, and to determine whether these changes are associated with recovery from anemia and severity of treatment-related adverse effects.
Animals
29 client-owned dogs with non-associative IMHA.
Methods
Dogs with IMHA underwent clinical monitoring, with collection of residual blood samples at serial time points. Expression of immune and glucocorticoid-regulated genes was quantified using real time quantitative polymerase chain reactions, with serum cytokine concentrations measured using multiplex arrays.
Results
Several clinical and gene expression variables changed with time in dogs with IMHA undergoing treatment, and we identified 6 major clusters representing different patterns of temporal change. No candidate dynamic variables were associated with more rapid recovery from anemia, but early increases in serum alkaline phosphatase (ALP) activity were associated with severity of later polydipsia.
Conclusions
Immune and clinicopathological variables are highly changeable after onset of treatment in dogs with IMHA, with early increases in serum ALP activity being associated with later severity of polydipsia. This parameter is therefore a key candidate for further investigations of individualization of immunosuppressive therapy for dogs with IMHA.