P.18Comparing histological features and molecular gene expression in anti-Jo1-, anti-PL-7 and anti-PL-12 antibody-positive patients

Abstract

Some subgroups of idiopathic inflammatory myopathies are defined by myositis-specific autoantibodies, like the anti-synthetase syndrome (ASyS). These specific antibodies describe subsets of patients with distinct clinical phenotypes reflecting an underlying antigen-driven process, e.g. Jo-1 myositis is characterized by perifascicular necrosis, inflammation with MHC expression and unique myonuclear actin inclusions. The most frequently detected antibodies other than Jo1 are PL-7 and PL-12 also affecting a considerable proportion of patients. However, beyond some clinical descriptions there exist no in-depth characterization of PL-7/PL-12 ASyS. Therefore, we focused on the detailed description of these subgroups, analyzing 40 patients using modern histopathology, qPCR, and electron microscopy to describe the disease more precisely. Besides clinical information, e.g. muscle affection, lung involvement, we quantified various morphological features like atrophy, necrosis, regeneration, MHC expression and cell infiltration. Of special interest are invading B and P cells, which we aim to characterize in combination with their attracting chemokines like CXCL13 or CXCR4. All three groups show similar histological features, but it became apparent that Jo1+ patients show a worse and more acute picture than PL-7/PL-12+ patients. In line with this results of the underlying immune response experiments with qPCR showed an upregulation of genes involved in a pro-inflammatory immune response in Jo1 (like strong upregulation of IFNG), whereas PL-7/PL-12 show a significantly increased expression of genes that are rather anti-inflammatory (e.g. upregulation of IL4R, TGFB). In conclusion, Jo1+ patients show different clinical features and appear more acute regarding the ongoing inflammation than PL-7/PL-12. Since the latter groups appeared very similar in terms of severity and accessory symptoms, they should be treated differently than Jo1+ patients regarding diagnostics and therapy.