Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Abstract

Importance: Current pathological criteria of dermatomyositis (DM) do not recognize different features among DM subtypes classified by dermatomyositis-specific antibodies (DMSAs). Objective: To determine whether myopathological features differ among DM subtypes classified by DMSAs and whether the pathological features can be characterized by serologically defined DM subtype. Design: Retrospective review of muscle pathology slides of 256 patients diagnosed with DM from January 2009 to December 2020. Setting: Single center study in a tertiary laboratory for muscle diseases. Participants: A total of 256 patients whose DM diagnosis was pathologically confirmed based on the sarcoplasmic expression of myxovirus resistant protein A (MxA) were included. Of these, 249 patients were positive for one of the 5 DMSAs (seropositive patients, anti-TIF1-γ=87, anti-Mi-2=40, anti-MDA5=29, anti-NXP-2=83, and anti-SAE=10), and 7 were negative for all 5 DMSAs (seronegative patients). Exposure: Histochemical, enzyme histochemical, immunohistochemical staining, and ultrastructural study. Main outcomes and measures: Histological features stratified according to four pathology domains: muscle fiber, inflammatory, vascular, and connective tissue domains, and histological features of interest by histochemistry, enzyme histochemistry, and immunohistochemical study commonly used in the diagnosis of inflammatory myopathy. Results: DMSAs significantly associated with characteristic histochemical and immunohistochemical features were as follows: anti-TIF1-γ with vacuolated/punched out fibers (64.7%, P<.001) and perifascicular enhancement in HLA-ABC (75.9%, P<.001); anti-Mi-2 with prominent muscle fiber damage (score 4.8±2.1, P<.001), inflammatory cell infiltration (score 8.0±3.0, P=.002), perifascicular atrophy (67.5%, P=.02), perifascicular necrosis (52.5%, P<.001), increased perimysium alkaline phosphatase activity (70.0%, P<.001), central necrotic peripheral regenerating fibers (45.0%, P<.001), and sarcolemmal deposition of the membrane attack complex (67.5%, P<.001); anti-MDA5 with scattered/diffuse staining pattern of MxA (65.5%, P<.001) with less muscle pathology and inflammatory features; and anti-NXP2 with microinfarction (26.5%, P<.001); and anti-SAE and seronegative DM with HLA-DR expression (50.0%, P=.02 and 57.1%, P=.02 respectively). Conclusion and relevance: We described an extensive study on serological-pathological correlation of DM primarily using MxA expression as an inclusion criterion. DMSAs was associated with distinctive myopathological features in our studied cohort, suggesting that different pathobiological mechanisms may underscore each subtype.

Muscle pathology of antisynthetase syndrome according to antibody subtypes

“…12 However, perifascicular HLA-DR expression was also observed in six ASS cases with normal/nonspecific pathology, suggesting that the expression was likely induced by high levels of serum IFN-γ. 47 Unlike DM, in which TRIs are ubiquitous (100%), these inclusions are present in subpopulations of ASS (47%-60%) 19,48 . Since TRIs can be induced in cultured endothelial cells by type I IFN (IFN1: IFN-α and IFN-≥) 49 , the number of TRIs in ASS can also be explained by a lower expression level of genes involved in the IFN1 pathway.…”

“…19 Sarcolemmal membrane attack complex deposition, both in general and in perifascicular areas, is more common in ASS than in DM (47.2% vs. 26.6% and 30.2% vs. 12.5%, respectively). 48…”

Pathophysiologische Mechanismen und Behandlung von Dermatomyositis und immunvermittelten nekrotisierenden Myopathien: Ein fokussiertes Review

“…Sie zeigen durchweg eine Überexpression von perifaszikulärem Myxovirus resistant A (MxA), einem Interferon (IFN-1)-induzierten Protein vom Typ I (Abb 1) [2, 30, 31]. Die Expression von MxA in Myofasern ist bei DM sehr spezifisch, was darauf hindeutet, dass es eine wichtige Rolle in der Pathophysiologie von DM spielt [32-34]. Die Ursache für die pathologischen Veränderungen in den perifaszikulären Muskelfasern ist noch nicht ganz klar: Sie könnten auf die Expression von IFN-1-induzierten Genprodukten oder auf Ischämie aufgrund von Kapillarverarmung oder auf eine Mischung aus beidem zurückzuführen sein [35-37].…”

“…DM ist mit 5 MSAs verbunden, nämlich Anti-TIF1-γ, Anti-MDA-5, Anti-SAE-1, Anti-Mi-2 und Anti-NXP-2 (Tabelle 2). Die Entdeckung der Dermatomyositis-spezifischen Antikörper (DMSAs) führte zu wertvollen Erkenntnissen über die unterschiedlichen Merkmale, die mit den verschiedenen Antikörpern verbunden sind [32]. Die relativen Anteile von DMSAs können zwischen Ländern und Kontinenten variieren.…”

“…Es werden Magen-, Lungen-, Brust-, Speiseröhren-, Blasen-, Kolorektal-, Eierstock- und Thymustumoren gefunden. Interessant ist, dass Anti-TIF1-γ-DM auch bei jüngeren Patienten (<40 Jahre) mit Malignität assoziiert ist [32].…”