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. 2014 Oct 23:2:154.
doi: 10.1186/s40478-014-0154-2.

Myofiber HLA-DR expression is a distinctive biomarker for antisynthetase-associated myopathy

Jessie Aouizerate, Marie De Antonio, Guillaume Bassez, Romain K Gherardi, Francis Berenbaum, Loïc Guillevin, Alice Berezne, Dominique Valeyre, Thierry Maisonobe, Odile Dubourg, Anne Cosnes, Olivier Benveniste, François Jérôme Authier  1
Affiliations

Myofiber HLA-DR expression is a distinctive biomarker for antisynthetase-associated myopathy

Jessie Aouizerate et al. Acta Neuropathol Commun. .

Abstract

Objectives: 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.

Conclusion: 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.

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Figures

Figure 1
Figure 1
Myopathological features in ASM (A, C, E, G) and DM (B, D, F, H). A: Myofiber injuries in ASM predominate in perifascicular areas (arrows) with the rounded atrophic appearance of regenerating myofibers; inflammatory infiltrates are mainly observed in perimysium and perifascicular endomysium and are associated with fragmentation of perimysium (asterisk). B: Perifascicular atrophy in DM characterized bymyofibers in peripheral regions of fascicles with a cross-sectional area substantially lower than in the rest of the fascicle(arrows). C: Myofiber NCAM expression (arrows) typically restricted to perifascular layers in ASM. D: In DM, NCAM-expressing myofibers are both perifascular (arrows) or grouped in foci (arrowheads). E, F: Diffuse myofiber reexpression of HLA-ABC in ASM (E) and DM (F), with marked perifascicular reinforcement in ASM (E). G, H: Macrophages in perimysium in the vicinity of fascicles (arrows) in ASM (G), and in perimysium (arrows) and perivascular areas (arrowhead) in DM (H). Frozen sections; hematoxylin-eosin (A, B) and immunoperoxidase technique for NCAM (C, D), HLA-ABC (E, F) and CD68 (G, H).
Figure 2
Figure 2
Comparison of myopathological lesions in DM (A, B) and ASM(C). A: Myosinolysis defined by the presence of punched-out vacuoles (arrows) or myofibrillar rarefaction areas, corresponding to foci of myosin filament proteolysis. B: Microinfarcts defined by numerous contiguous fibres within a fascicle, at the same stage of necrosis or regeneration. C: Perimysial fragmentation defined by focal clear areas (asterisk) and spumous appearance of adjacent areas (arrowhead). D: Percentages of cases with presence of the lesion (perimysial fragmentation, microinfarcts, vacuoles, and perifascicular atrophy) in ASM and DM. (*) indicates p < 0.05.Frozen sections (A-C); hematoxylin-eosin (A, B) and Masson trichrome (C).
Figure 3
Figure 3
HLA-DR expression and C5b-9 deposition in ASM and DM. A-F: Regular myofiber HLA-DR expression in perifascicular areas in ASM (A, C-F) contrasting with the lack or very few number of positive myofibers in DM (B); positive staining of endomysial vessels (arrows) is physiological (C). G, H: C5b-9 deposition observed at the surface of perifascicular myofibers in ASM (G) and in endomysial vessel walls (arrows) in DM (H). I,J: Percentage of HLA-DR-positive myofibers (I) and of contiguous HLA-DR-positive perifascicular myofibers (J) in ASM and DM. K: Percentages of cases with presence of C5b-9 deposition at the surface of non-necrotic myofibers in ASM and DM. (*) indicates p < 0.05.Frozen sections (A-H); immunoperoxidase technique for HLA-DR (A-F) and C5b-9 (G, H).
Figure 4
Figure 4
CD8+ T-cell infiltration and myofiber HLA-DR expression. A, B: Comparison of CD8+ T-cells infiltration and myofiber HLA-DR expression in a same case of ASM. CD8+ T-cells (arrows) are detected in perifascicular endomysium and adjacent perimysium (A), in the areas corresponding to those of the strongest myofiber HLA-DR expression (B). Frozen section; immunoperoxidase technique for CD8 and HLA-DR. C: Percentage of patients with a CD8+ score equal to 1 or 2, in ASM and DM; (*) indicates p < 0.05. D: Percentage of HLA-DR-positive myofibers according to the degree of CD8+ T-cell infiltration. Comparison was done between patients with a CD8+ score null and patients with score equal to 1 or 2, ASM and DM patients having been pooled.
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