Background/Purpose: Idiopathic inflammatory myopathies (IIM) are a group of heterogeneous disorders that typically present with proximal muscle weakness. According to the classification criteria, IMs are classified into five categories: polymyositis (PM); non-specific myositis (NSM); dermatomyositis (DM); necrotizing autoimmune myopathy (NAM); and sporadic inclusion body myositis (IBM), with further subgrouping by autoantibodies that are specific or non-specific to myositis. There is a need to develop optimal diagnostic and classification criteria with more reliable and reproducible markers of pathological and serological evidence for all subgroups of IIM.

Methods: Following ethical approval, paraffin- and frozen sections from muscle biopsies of patients meeting inclusion criteria and controls (patients with no diagnostic abnormalities on muscle biopsy) were obtained. The sections were stained with hematoxylin and eosin (H&E), membrane attack complex (MAC) C5b–9, and major histocompatibility complex (MHC) class I for CD59, CD55, and CD46. A blinded examination was then achieved by randomly mixing the specimen numbers. 

Results: CD46, CD55, and CD59 were differentially expressed in endomysial capillaries and myofibers. Whereas CD59 was expressed in endomysial capillaries as well as myofibers, CD46 expressed in capillaries only, and CD55 expression was prominent in myofibers and only equivocal in capillaries. MAC C5b-9 pathological expression correlated with significant reduction of expression of membrane-bound complement regulators. 

In DM, MAC C5b-9 deposition is present mainly in perifascicular endomysial capillaries with corresponding clear downregulation of CD59 and CD46, mainly in perifascicular areas. This and earlier findings suggest that much of the ischemic/inflammatory effect in DM is complement-mediated and related to classical pathway complement activation on capillary endothelium that is not protected by membrane-bound complement regulators. This early event in the process of injury occurs prior to inflammatory cell infiltrate.

In PM, MAC C5b-9 deposition in the general group of PM is in necrotic myofibers; however, there was clear but less pronounced staining in capillaries with weaker downregulation of membrane-bound regulatory proteins.

Conclusion: Complement activation should be determined in each subgroup of IIM

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/classifications-of-inflammatory-myopathies-differentially-expressed-membrane-bound-complement-regulators-allow-specific-patterns-of-membrane-attack-complex-deposition/