Expression and significance of non-canonical pyroptosis pathway-related proteins in muscle tissues of patients with dermatomyositis/polymyositis / 中华微生物学和免疫学杂志

ABSTRACT

Objective:To detect the expression of cysteinyl aspartate specific proteinase 4 (caspase-4), caspase-5, gasdermin D (GSDMD), nucleotide-binding oligomerization domain-like receptor protein-3 (NLRP3), Pannexin-1 and P2X7 involved in non-canonical pyroptosis pathway in muscle tissues of patients with dermatomyositis (DM)/polymyositis (PM) and to investigate the roles and significance of them in the pathogenesis of DM and PM.Methods:Altogether 13 DM patients, nine PM patients and 20 volunteers (control group) treated in the Affiliated Hospital of Qinghai University from January 2019 to September 2020 were enrolled in the present study. The 20 volunteers with no additional concomitant diseases underwent debridement due to simple orthopedic trauma. Pathological changes in muscle tissues were detected by hematoxylin & eosin (HE) staining. Expression of caspase-4, caspase-5, GSDMD, NLRP3, Pannexin-1 and P2X7 in muscle tissues was measured using immunohistochemistry (IHC).Results:(1) HE staining results showed that the muscle fibers in the control group had basically normal morphology and structure with no obvious inflammatory cell infiltration, atrophy, degeneration or necrosis. However, the size and thickness of muscle fibers in DM and PM groups were different with excessive inflammatory cell infiltration, atrophy, degeneration and necrosis to varying degrees. Moreover, the pathological scores of HE staining in muscle tissues of DM and PM groups were significantly higher than that of the control group and the differences were of statistical significance ( P<0.05). (2) IHC staining results suggested that the expression of caspase-4, caspase-5, GSDMD, NLRP3, Pannexin-1 and P2X7 in muscle tissues was higher in DM and PM groups than in the control group ( P<0.05). (3) As indicated by Pearson correlation analysis, the pathological scores of HE staining in muscle tissues of DM and PM groups were positively correlated with the IHC scores of caspase-4, caspase-5, GSDMD, NLRP3, PAnnexin-1 and P2X7 ( P<0.05). Furthermore, the IHC scores of caspase-4 and caspase-5 were positively correlated with the IHC scores of GSDMD and Pannexin-1 ( P<0.05); the IHC score of GSDMD was positively correlated with the IHC score of NLRP3 ( P<0.05); the IHC score of Pannexin-1 was positively correlated with the IHC score of P2X7 in muscle tissues ( P<0.05). Conclusions:The non-canonical pyroptosis pathway might be involved in the pathogenesis of DM and PM, which was possibly achieved by promoting inflammatory response. These results suggested that the non-canonical pyroptosis pathway played crucial roles in the immune pathogenesis of DM and PM.