Chronic Graft Versus Host Myopathies: Noninflammatory, Multi-Tissue Pathology With Glycosylation Disorders

Abstract

Abstract Myopathies during chronic graft-versus-host disease (cGvHD) are syndromes for which tissue targets and mechanisms of muscle damage remain incompletely defined. This study reviewed, and pathologically analyzed, 14 cGvHD myopathies, comparing myopathology to other immune myopathies. Clinical features in cGvHD myopathy included symmetric, proximal weakness, associated skin, gastrointestinal and lung disorders, a high serum aldolase (77%), and a 38% 2-year survival. Muscle showed noninflammatory pathology involving all 3 tissue components. Perimysial connective tissue had damaged structure and histiocytic cells. Vessel pathology included capillary loss, and reduced α-l-fucosyl and chondroitin sulfate moieties on endothelial cells. Muscle fibers often had surface pathology. Posttranslational glycosylation moieties on α-dystroglycan had reduced staining and abnormal distribution in 86%. Chondroitin-SO4 was reduced in 50%, a subgroup with 3-fold longer times from transplant to myopathy, and more distal weakness. cGvHD myopathies have noninflammatory pathology involving all 3 tissue components in muscle, connective tissue, small vessels, and myofibers. Abnormal cell surface glycosylation moieties are common in cGvHD myopathies, distinguishing them from other immune myopathies. This is the first report of molecular classes that may be immune targets in cGvHD. Disordered cell surface glycosylation moieties could produce disease-related tissue and cell damage, and be biomarkers for cGvHD features and activity.