{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:01:56Z","timestamp":1789610516392,"version":"build-2803163510"},"posted":{"date-parts":[[2025,2,21]]},"group-title":"Rheumatology","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Myositis is a heterogeneous family of inflammatory myopathies. We sought to define the differential expression of cytokines, cytokine receptors, and immune checkpoint genes in muscle biopsies from patients with different forms of myositis in order to characterize patterns of inflammation in each.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Bulk RNA sequencing was performed on muscle biopsy samples from 669 patients, including 105 with dermatomyositis, 80 with immune-mediated necrotizing myopathy (IMNM), 65 with anti-synthetase syndrome, 53 with inclusion body myositis (IBM), 19 with anti-PM\/Scl myositis, 310 with other inflammatory or genetic myopathies, and 37 controls with normal tissue (NT). Myositis clinical groups and autoantibody subgroups were analyzed separately. Expression data was analyzed for 338 genes encoding cytokines, cytokine receptors, and immune checkpoints. Myositis group-specific genes were identified from this list by finding genes that were specifically differentially expressed in one group compared to all samples and compared to NT (\u03b1&lt;0.001).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    IBM patients had the most differentially overexpressed genes (71) among all clinical groups, including 37 that were IBM-specific. Among the top genes were several involved in type 1 inflammation, including\n                    <jats:italic>CCL5<\/jats:italic>\n                    ,\n                    <jats:italic>CXCR3<\/jats:italic>\n                    ,\n                    <jats:italic>CCR5<\/jats:italic>\n                    ,\n                    <jats:italic>CXCL9<\/jats:italic>\n                    , and\n                    <jats:italic>IFNG<\/jats:italic>\n                    . Anti-Jo1 and anti-PM\/Scl patients exhibited differential overexpression of a similar set of genes, while dermatomyositis patients exhibited differential overexpression of a different set of genes involved in type 1 inflammation. IMNM patients had the least number of differentially overexpressed genes with no predominant inflammatory pattern.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Each myositis clinical group and autoantibody subgroup had differentially overexpressed inflammatory mediators, including a strong type 1 inflammatory gene signature in IBM.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key Messages<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Inclusion Body Myositis (IBM) muscle biopsies exhibit differential overexpression of a set of genes involved in type 1 inflammation.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        The\n                        <jats:italic>CCL5<\/jats:italic>\n                        -\n                        <jats:italic>CCR5<\/jats:italic>\n                        and\n                        <jats:italic>XCL1<\/jats:italic>\n                        -\n                        <jats:italic>XCL2<\/jats:italic>\n                        -\n                        <jats:italic>XCR1<\/jats:italic>\n                        axes are specifically differentially overexpressed in IBM muscle and may contribute to T\n                        <jats:sub>C<\/jats:sub>\n                        1-mediated inflammation.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Dermatomyositis, anti-Jo1 myositis, and anti-PM\/Scl myositis muscle biopsies also exhibit overexpression of type 1 inflammatory genes, but to a lesser extent than IBM.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n    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