10PAnti-synthetase syndrome - finding a pearl in an oyster: a series of 12 cases

Abstract

Anti-synthetase syndrome (ASS), a heterogenous inflammatory myopathy, is a rare autoimmune disorder associated with specific autoantibodies, particularly anti-Jo1, targeting aminoacyl-tRNA synthetases (ARS). Clinical manifestations often lead to diagnostic confusion due to overlap with dermatomyositis, polymyositis and other autoimmune diseases. An analysis of 12 Anti-Synthetase syndrome (ASS) cases was done from 2019-2024. Muscle biopsy examination and a 16 antigen Euroline immunoblot was done for myositis specific and associated antibodies, including Mi-2a, Mi-2b, TIF1g, MDA5, NXP2, SAE1, Ku, PMScl100, PMScl75, Jo-1, SRP, PL-7, PL-12, EJ, OJ and Ro52. The mean age was 43.3 years (range 22-68 years) with a male: female ratio of 1:11. Clinical features included proximal muscle weakness (100%), arthritis (58%), Raynaud’s phenomenon (33%), fever (66%) and interstitial lung disease (16%). On muscle biopsy examination, 83% showed variation in fascicular size, 50% showed perifascicular atrophy, 66% showed degenerating and regenerating fibres and 50% showed inflammatory cells, predominantly CD3 and CD8 positive T cells. On immunohistochemistry, 83% showed MHC I upregulation, 50% showed MHC II upregulation on myofibres, 41% showed both and 100% showed fine granular MAC deposition on endomysial blood vessels. On immunoblot, Jo-1 was positive in 58%, PL7 in 16%, PL12 in 25% and Ro52 in 75% cases. One case was positive for dermatomyositis specific antibody (TIF-1g) also.It is important to evaluate ASS specific antibodies in all cases of IIM, even with the suspicion of dermatomyositis or polymyositis. The limited awareness about ASS can lead to delayed diagnosis and treatment requiring intensive immunosuppression.