OP0032 Is immunohistochemistry useful to predict response to treatment in necrotizing myopathies?
Authors: S Fernandes, B Lopez, P Gordon, S Al-Sarraj
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Muscle biopsy is the gold standard for the diagnosis of inflammatory myopathies, but the role of immunohistochemistry in Necrotizing Myopathies (NM) has not been fully characterized yet. <h3>Objectives</h3> To determine if MHC-I expression and pattern of C5b-9 deposition in capillaries correlate with clinical phenotype and response to treatment in NM. <h3>Methods</h3> The Neuropathology Departmental database was searched to identify patients with a histological diagnosis of NM and follow up data for at least 6 months (30 patients). Electronic patient records were reviewed retrospectively to record demographics, autoantibodies, treatment, proximal muscle power at 3, 6 and 12 months by Manual Muscle Testing (MMT) (2), levels of CK and flares. Patients were classified as responders when there was improvement of MMT ≥20% and non-responders when MMT improvement was &lt;20% (3). All biopsies were reviewed blindly by an experienced neuropathologist. MHC-I expression was classified as positive only if over expressed in all fibers. The patterns of C5b-9 deposition in endomysial capillaries were classified as specific (solid), non-specific (granular) or negative. <h3>Results</h3> MHC-I positive group (n=16/30) had a higher proportion of responders (62,5% vs 7,7%, p=0.002), higher number of patients with total recovery of muscle power (66,7 vs. 15,4%) and were more commonly positive for autoantibodies (75% vs. 35.7%, p=0.030) when compared to the MHC-I negative group (n=14). 17 patients were positive for auto-antibodies of which 9 were myositis specific antibodies [SRP (n=6), HMG-CoA reductase (n=1), Jo-1 (n=1), P155/140 (n=1)] and 4 were myositis associated antibodies [Ro-52 (n=2), Ku (n=1), Pm/Scl (n=1)]. 13/30 patients had C5b-9 deposition, with a specific pattern in 5 and non-specific in 8. The specific pattern group had a greater reduction of CK after 6 months compared to non-specific and negative respectively (98% vs. 77% vs. 56.8%, p=0.006), greater reduction in CK after 12 months (96.6% vs. 68.9% vs. 59.6%, p=0.024) and higher rates of responders (80% vs. 60% vs. 18,8%, p=0.001). Six patients were on immunosuppressants (azathioprine/hydroxychloroquine, n=2), steroids (n=3) or both (n=1) for a minimum of 4 weeks when the biopsy was performed. Differences in age, gender, clinical features or treatment were not found to be statistically significant. <h3>Conclusions</h3> Upregulation of MHC I and solid staining pattern of C5b-9 in the capillaries of NM patients appears to be associated with a better outcome. <h3>References</h3> Cong L, Pu CQ, Shi Q, Wang Q, Lu X, Complement membrane attack complex is related with immune-mediated necrotizing myopathy, Int J Clin Exp Pathol 2014;7(7):4143–41499. Rider LG, Koziol D, Giannini EH, Jain MS, Smith MR, Whitney-Mahoney K, Feldman BM, Wright SJ, Lindsley CB, Pachman LM, Villalba ML, Lovell DJ, Bowyer SL, Plotz PH, Miller FW, Hicks JE. Vencovsky J, New ACR/EULAR Criteria for Myositis, Ann Rheum Dis 2015;74:42–43. <h3>Disclosure of Interest</h3> None declared