34PCharacterization of inflammatory infiltrate in inclusion body myositis and its comparison with other IIMs

Inclusion body myositis (IBM) is an inflammatory autoimmune disorder of skeletal muscle affecting patients over the age of 40, with distinctive clinical and histopathological features. A direct cause of

IBM muscle damage is T cell–mediated cytotoxicity of IBM myofibers. On muscle biopsy, IBM is characterized by a peculiar combination of endomysial inflammation, rimmed vacuoles, and protein aggregation. This ambispective observational study included 26 patients biopsy proven IIMs cases over a period of six years. Both retrospective and prospective data were collected, including detailed clinical profiles, laboratory parameters, and histopathological features. To further characterize the nature of the inflammatory infiltrate, confocal microscopy was performed using a panel of nine inflammatory cell markers: CD3, CD4, CD8, CD16, CD56, CD68, CD86, CD163 and KLRG1. These markers were analyzed in dual combinations. Twenty-six biopsy proven patients of IIMs (16 IBM + 8 DM + 1OM + 1IMNM) were included in this study. The baseline demographics included age 36-72 years, (Male:Female;16:10). Clinically differential diagnosis included inflammatory and metabolic myopathies, LGMD, SLE with myopathy. Histopathological features in inclusion body myositis included loss of fascicular architecture (12/16 cases), rimmed vacuoles (8/16 cases), variation in fibre size (all 16 cases) and inflammatory infiltrate in all 16 cases with CD3 and CD8 positivity in 14/16 cases, and two cases with CD3 and CD4 positivity. Dermatomyositis features included loss of fascicular architecture (6/8 cases), Perifascicular atrophy (5/8 cases), variation in fiber size (8/8 cases), chronic inflammatory infiltrate (6/8 cases; with CD3 and CD8 positive cells in 4/8 cases, CD3, CD4 and CD8 positive cells in 2/8 cases). Single case of IMNM showed maintained fascicular architecture with mild variation in size, along with few degenerating fibers. On confocal microscopy 6/16 IBM cases showed inflammatory cells with dual positivity for CD3 and CD8, 5/16 IBM cases showed KLRG1 positive cells out of which single case showed dual positivity for CD8 and KLRG1, 3/16 IBM cases showed CD68 positive cells while all IBM cases were negative for CD16, CD56, CD86, and CD163 inflammatory markers. On confocal 3/8 dermatomyositis cases showed dual positivity for CD3 and CD8 markers, and single cases showed cells positive for CD16, CD68, and KLRG1, respectively. While all dermatomyositis cases were negative for CD86, CD163, and CD56 inflammatory markers. The IMNM case exhibited a complete absence of inflammatory cells. In comparison, the overlap myositis case showed selective infiltration by CD3-positive cells, with all remaining markers remained negative. In our analysis, inclusion body myositis showed prominent infiltration by CD8+ and KLRG1+ highly differentiated T cells, a pattern not observed in dermatomyositis or other IIMs. Given the limited response to steroid treatment in IBM, these cell populations could serve as potential targets for alternative therapies.