title: Myofiber HLA-DR expression is a distinctive biomarker for antisynthetase-associated myopathy.
abstract: OBJECTIVE
  To assess the value of major histocompatibility complex (MHC) class II antigen (HLA-DR) expression to distinguish anti-synthetase myopathy (ASM) from dermatomyositis (DM).
  
  
  METHODS
  Muscle biopsies from patients with ASM (n = 33), DM without anti-synthetase antibodies (ASAb) (n = 17), and normal muscle biopsy (n = 10) were first reviewed. ASAb included anti-Jo1 (26/33), anti-PL12 (4/33), anti-PL7 (2/33), and anti-EJ (1/33). Immunohistochemistry was performed for MHC-I/HLA-ABC, MHC-II/HLA-DR, membrane attack complex (C5b-9), neural cell adhesion molecule (NCAM)/CD56 expression, and inflammatory cell subsets. Twenty-four ASM and 12 DM patients from another center were added for HLA-DR evaluation.
  
  
  RESULTS
  Ubiquitous myofiber HLA-ABC expression was equally observed in ASM and DM (93.9% vs 100%, NS). In contrast, myofiber HLA-DR expression was found in 27/33 (81.8%) ASM (anti-Jo1: 23/26, 88.5%; others: 5/7, 71.4%) vs 4/17 (23.5%) DM patients (p < 0.001). HLA-DR was perifascicular in ASM, a pattern not observed in DM. In addition, C5b-9 deposition was observed on sarcolemma of non-necrotic perifascicular fibers in ASM, while, in DM, C5b-9was mainly detected in endomysial capillaries. CD8 cells were more abundant in ASM than in DM (p < 0.05), and electively located in perimysium or in perifascular endomysium. HLA-DR expression correlated positively with the CD8+ cells infiltrates. Strictly similar observations were made in the confirmatory study.
  
  
  CONCLUSIONS
  ASM is characterized by strong myofiber MHC-II/HLA-DR expression with a unique perifascicular pattern, not described so far. HLA-DR detection must be included for routine myopathological diagnosis of inflammatory/dysimmune myopathies. HLA-DR expression in ASM may indicate a specific immune mechanism, possibly involving IFNγ.
authors.forename: Jessie
authors.initials: J
authors.lastname: Aouizerate
authors.forename: Marie
authors.initials: M
authors.lastname: De Antonio
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bassez
authors.forename: Romain K
authors.initials: RK
authors.lastname: Gherardi
authors.forename: Francis
authors.initials: F
authors.lastname: Berenbaum
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillevin
authors.forename: Alice
authors.initials: A
authors.lastname: Berezne
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.forename: Thierry
authors.initials: T
authors.lastname: Maisonobe
authors.forename: Odile
authors.initials: O
authors.lastname: Dubourg
authors.forename: Anne
authors.initials: A
authors.lastname: Cosnes
authors.forename: Olivier
authors.initials: O
authors.lastname: Benveniste
authors.affiliation: Reference Center for Neuromuscular Diseases, Hôpital Henri Mondor, APHP, Créteil, France. authier@u-pec.fr.
authors.forename: François Jérôme
authors.initials: FJ
authors.lastname: Authier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D003882:Dermatomyositis / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009220:Myositis / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D006684:HLA-DR Antigens