1151 - A Novel Autoantibody against 200/100 Kd Proteins Is Associated with Necrotizing Myopathy

Monday, October 19, 2009: 11:15 AM
Ballroom AB (Pennsylvania Convention Center)
Lisa Christopher-Stine, Grace Hong, Livia Casciola-Rosen, Andrea M. Corse and Andrew Mammen, Johns Hopkins University School of Medicine, Baltimore, MD
Presentation Number: 1151

Purpose: The inflammatory myopathies are a family of conditions characterized by proximal muscle weakness, elevated serum muscle enzymes, and inflammatory infiltrates on muscle biopsy. However, ~20% of patients with clinical features of myositis do not have a significant degree of inflammation on muscle biopsy. Instead, biopsies from these patients demonstrate numerous degenerating, necrotic, and regenerating myofibers. Necrosis may be seen in patients with muscular dystrophies or toxic exposure as well as in those patients with myositis specific autoantibodies (MSAs). Nevertheless, a substantial proportion of patients with necrotizing myopathies have none of these known associations. We sought to determine novel autoantibody associations in patients with predominately necrotic features in the absence of substantial inflammatory infiltrates on muscle biopsy. Method: 225 patients in the Johns Hopkins Myositis Cohort had both a muscle biopsy available for review at our institution and banked serum. Biopsies were evaluated for the presence of inflammation, regeneration, degeneration, necrosis, and vacuolar change. Antibody specificities in patient sera were assessed by performing immunoprecipitations from 35S-methionine labeled HeLa cell lysates. Results: 38 patients in the JHU Myositis Cohort had predominant necrosis on muscle biopsy without histologic findings of perifascicular atrophy or red-rimmed vacuoles. Sera from these patients were screened by immunoprecipitation for the presence of novel autoantibodies. 12 patients had known autoantibody association or other diagnoses [SRP (6), anti-Jo-1(1), 1 anti-PL12 (2), anti-PL-7 (1), profound hypothyroidism(1), and dysferlinopathy(1)]. The remaining 26 patients had no known MSAs or other diagnosis to explain the necrotizing myopathy. A novel autoantibody specificity was found in 16 of these 26 patients (62%). These sera immunoprecipitated a pair of proteins with molecular weights of 100 kDa and 200 kDa. In contrast, control human sera did not precipitate these or other proteins. Only one additional patient with this autoantibody specificity was identified among 197 patients without prominent features of necrosis on muscle biopsy. Conclusion: We have identified a novel autoantibody specificity which is associated with characteristic muscle biopsy findings and a variable clinical phenotype. Since we have not found instances of sera which precipitated only one of these proteins, we hypothesize that these may be subunits of a protein complex. Our findings show that patients with anti-200/100 represent a distinct subgroup of necrotizing myopathy patients that were previously considered to be “autoantibody negative.” Future studies will be directed towards identifying the autoantigens recognized by these autoantibodies.

Keywords: autoantibodies and myositis

Disclosure: L. Christopher-Stine, None; G. Hong, None; L. Casciola-Rosen, None; A. M. Corse, None; A. Mammen, None.