Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune‐Mediated Myositis

Abstract

BackgroundMajor histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune‐mediated myositis (IMM) of humans and dogs and in dysferlin‐deficient muscular dystrophy.Hypothesis/ObjectivesTo determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM.AnimalsTwenty‐one IMM horses of Quarter Horse‐related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase‐resistant polysaccharide storage myopathy [PSSM]).MethodsImmunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a‐sarcoglycan was performed.ResultsSarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a‐sarcoglycan staining were similar in IMM and control muscles.Conclusions and clinical importanceDeficiencies of dysferlin, dystrophin, and a‐sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune‐mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates.

Clinical Implications and Hospital Outcome of Immune‐Mediated Myositis in Horses

“…Based on immunophenotyping, predominant CD4+ followed by CD8+ T‐lymphocytes, a cellular immune response was responsible for the observed myonecrosis. This finding was similar to that described in previous studies in horses . In our study, CD20+ B‐lymphocytes were not a major component of this suspected autoimmunity.…”

“…Monitoring of renal variables is important because renal insult resulting in failure is a potential complication. Although IMM can occur can in horses of various breeds, Quarter horses and related breeds seem to be predisposed . Therefore, a familial or genetic bases for the development of disease must be considered in this breed.…”

“…The primary laboratory findings include increase in creatine kinase and aspartate aminotransferase activity on a serum biochemistry panel . The main histological feature of skeletal muscle biopsies is mononuclear cell infiltration of predominantly CD4+ T‐lymphocytes and myonecrosis . Immune‐mediated myositis belongs to a group of inflammatory myopathies .…”

“…Inflammatory myopathies in dogs include muscle masticatory myositis, extraocular myositis, dermatomyositis‐like, polymyositis, and overlap syndrome . Peer review reports of IMM in horses are limited . Causes of IMM in horses have not been fully elucidated, but temporal relationships have been ascribed to autoimmunity developed to bacterial or viral antigens .…”

Streptococcus equiInfections in Horses: Guidelines for Treatment, Control, and Prevention of Strangles—Revised Consensus Statement

“…Significant rhabdomyolysis with muscle atrophy has been identified in 4 Quarter Horses after exposure to S. equi . Some of these horses had underlying polysaccharide storage myopathy and developed rhabdomyolysis while ill. Others developed myositis without an underlying problem and exhibited malaise and a rapidly progressive atrophy of the epaxial and gluteal muscles.…”