POS0490 USEFULNESS OF MHC-II IMMUNO-STAINING ON MUSCLE BIOPSIES IN IDIOPATHIC INFLAMMATORY MYOPATHIES

Abstract

BackgroundIdiopathic inflammatory myopathies (IIMs) constitute a group of acquired muscular diseases that occur during childhood and adulthood, exhibit a variety of phenotypes and are potentially life-threatening. IIM diagnosis considers clinical, serological, and histological data. Muscle pathological analysis of IIM patients gives relevant elements for the diagnosis (immune cell infiltrate, vascular and connective tissues, as well as myofiber morphology). Immunochemistry (IHC) labeling for major histocompatibility complex class I (MHC-I), and C5b9, that are negative in normal muscle, appeared of interest in IIM diagnosis and the understanding of IIM pathogenesis. In normal muscle, myofibers are negative for MHC-II IHC. Its interest in the neuropathological exam of IIM muscle remains to be better characterized.ObjectivesThis study aims to analyze the pattern of MHC-II expression in various IIMs.MethodsA historical cohort was designed using the MYOLYON register (IIM patients diagnosed between 2016 and 2020 at the University Hospital of Lyon, France). Inclusion criteria were IIM diagnosis that was established histologically and available frozen muscle samples for additional analyses. Exclusion criterium was any treatment before muscle biopsy. Demographical data and final diagnosis were collected retrospectively from medical records. A centralized, standardized, and blind analysis of muscle MHC-II immuno-staining was conducted to define the various patterns of MHC-II by myofibers and by capillaries. The study complied with ethical requirements.ResultsSeventy-three patients were included: 23 dermatomyositis (DM), 13 anti-synthetase syndrome (ASS), 13 immune-mediated necrotizing myopathies (IMNM), 13 inclusion body myositis (IBM), and 11 overlap myositis (OM). MHC-II immuno-staining of myofibers or capillaries was abnormal for 91.8% of the analyzed biopsies (Figure 1). The analysis of MHC-II myofiber immuno-staining revealed distinguishable patterns according to IIM subtype: the labeling was diffuse in IBM (69.2%, n=9/13), perifascicular in ASS (61.5%, n=8/13), and variable in OM (patchy for 27.3% n=3/11 or clustered for 36.4%, n=4/11). MHC-II immuno-staining was negative in IMNM (84.6%, n=11/13) and in DM (47.8%, n=11/23). DM exhibiting positive MHC-II myofibers (n=12) were associated with the presence of anti-TIF1γ, anti-NXP2 and anti-SAE auto antibodies (n=5, n=3 and n=2, respectively). Among the 12 patients, there were juvenile cases (n=5, 41.7%) or DM associated with ongoing neoplasia (n=4, 33.3%). Three main architectures were described for capillaries: giant, leaky and capillary dropout. Patterns of MHC-II positive capillaries were the following: DM was characterized by capillary dropout (68.2%), IMNM showed leaky capillaries (75.0%), IBM giant capillaries (66.7%), ASS exhibited both giant (61.5%) and/or leaky (58.3%) capillaries, while OM showed giant (63.6%) or/and leaky (80.0%) capillaries and capillaries dropout (60.0%).ConclusionThe present work establishes the usefulness of MHC-II immuno-staining for IIM diagnosis, and gives additional elements on the impairment of myofibers and capillaries in the various IIM subgroups. MHC-II expression is known to be induced by inflammatory cytokine such as interferon type II. This could be linked to myofiber and/or capillary impairment in some IIMs, such as IBM, ASS and OM. These results also support the implication of vasculopathy in IIM pathogenesis, with various structural and cellular consequences regarding the different subgroups. Finally, MHC-II immuno-staining in IIM muscle biopsies enables a foremost analysis of myofibers and capillaries, and represents an additional biomarker to distinguish IIM subgroups.