Immune-Mediated Myositis in Horses: From phenotype to genotype

University of Minnesota M.S. thesis. May 2016. Major: Veterinary Medicine. Advisor: Stephanie Valberg. 1 computer file (PDF); x, 133 pages.Background: Equine immune-mediated myositis (IMM) is a painful and debilitating condition of predominantly Quarter Horse (QH) and related breeds. The epaxial and gluteal muscles are most severely affected and muscle atrophy can be dramatic, with 50% of the affected muscle mass being lost in <72 hours. Diagnosis is based on a muscle biopsy of affected muscles and the identification of lymphocytes invading myofibers and in some cases surrounding blood vessels. The pathophysiology is presumed to be immune-mediated, but further evidence is needed to confirm this. Abnormal expression of major histocompatibility Complex (MHC) has been identified on muscle fibers from most human IMMs and provides the most consistent indication of an immune-mediated mechanism. The restriction of IMM to primarily QH and related breeds, particularly in certain bloodlines suggests that there is a genetic susceptibility underlying IMM. Hypothesis: Quarter Horses are genetically susceptible to an immune mediated myositis that is characterized by abnormal expression of MHC class I and/or class II on the sarcolemma of myofibers. Specific Aim 1: To determine if abnormal MHC class I and II expression is present on the sarcolemma of myofibers of horses with active IMM in the presence or absence of myofiber lymphocytic infiltrates. Specific Aim 2: To characterize the subtypes of lymphocytes in the myofibers of horses with active IMM and correlate this with MHC expression. Methods: Immunohistochemical staining for MHC I, II, CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle samples of IMM (21 horses) and controls (3 healthy and 6 disease controls). Scores were given for MHC I and II and for lymphocytic subtypes. Results: A degree of sarcolemmal MHC I and II expression was present in 81% and 71% of IMM horses, respectively. CD4+, CD8+, and CD20+ cells were present in 20/21 IMM horses with a CD4+ predominance in 48% of cases. MHC I score was positively correlated with MHC II (r = 0.89, p = <0.001) and CD8+ (r= 0.64, p = 0.002) and CD20+ (r = 0.66, p = 0.001) lymphocyte and macrophage scores (r = 0.70, p = <0.001). MHC II scores were positively correlated to CD8+ (r = 0.59, p = 0.005), CD20+ (r = 0.61, p = 0.004) lymphocyte and macrophage (r = 0.70, p =