Histopathologic Findings in 5 Patients With Hypomyopathic Dermatomyositis

El-Dokla, Ahmed; Aggarwal, Rohit; Oddis, Chester V.; Ali, Sara T.; Lacomis, David

doi:10.1097/cnd.0000000000000098

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…Therefore MHC-I is considered as an effective molecular marker for PM. The increased level of MHC-I molecule in the skeletal muscle is associated with muscle fiber damage and/or induction of endoplasmic reticulum stress, contributing to muscle dysfunction [ 27 , 28 ]. Moreover, a previous study showed that the overexpression of MHC-I alone in the mice skeletal muscle could lead to a self-sustaining inflammatory process involving muscle fiber damage and infiltration of mononuclear cells with the most of the characteristic features of human PM, and suggested that the up-regulation of MHC-I may initiate a cascade of events typical of muscle inflammation in the spontaneous human disease [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome up-regulates major histocompatibility complex class I expression and promotes inflammatory infiltration in polymyositis

et al. 2022

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Objective This study was designed to investigate the role of the nucleotide-binding-domain -and leucine-rich repeat -containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome in the pathogenesis of polymyositis (PM). Methods Immunochemistry was performed to analyze the NLRP3, caspase-1 and interleukin-1 beta (IL-1β) expression in the muscle tissue of PM patients. Rat model of PM and C2C12 cell were used to investigate the potential role of NLRP3 inflammasome in PM. Results The percentage of CD 68+ macrophages, and the expression levels of NLRP3, caspase-1 and IL-1β in the muscle tissue were elevated in 27 PM patients. LPS/ATP treatment resulted in activation of NLRP3 inflammasome and secretion of IL-1β as well as interferons (IFNs) and monocyte chemotactic protein-1 (MCP-1) in the Raw 264.7 macrophages. Meanwhile, LPS/ATP challenged activation of NLRP3 inflammasome induced overexpression of major histocompatibility complex class I (MHC-I), a key molecular of PM in the co-cultured C2C12 cells. The effect was decreased by treatment of NLRP3 inflammasome inhibitor MCC950 or siRNA of NLRP3 inflammasome. These findings suggested certain levels of IL-1β rather than IFNs up-regulated MHC-I expression in C2C12 cells. IL-1β blockade using neutralizing IL-1β monoclonal antibody or siRNA of IL-1β suppressed MHC-I overexpression. In vivo, NLRP3 inflammasome inhibition by MCC950 reduced the expression of NLRP3, IL-1β and MHC-I in the muscle tissue of PM modal rats. Also, it attenuated the intensity of muscle inflammation as well as the CRP, CK, and LDH levels in the serum. Conclusion NLRP3/caspase-1/IL-1β axis may play an important role in the development of PM. Inhibition of NLRP3 activation may hold promise in the treatment of PM.

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Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome up-regulates major histocompatibility complex class I expression and promotes inflammatory infiltration in polymyositis

et al. 2022

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“…An atypical form of dermatomyositis is hypomyopathic dermatomyositis. Clinically amyopathic dermatomyositis (CADM) accounts for approximately 20% of dermatomyositis, which includes amyopathic dermatomyositis (ADM) and hypomyopathic dermatomyositis (HDM) 1,2 . The former refers to characteristic cutaneous manifestations without evidence of myopathy for two or more years.…”

Section: Introductionmentioning

confidence: 99%

A case of Hypomyopathic Dermatomyositis which subsequently developed to overt Myositis with ILD

2022

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Dermatomyositis (DM) is an inflammatory myositis. Clinically amyopathic dermatomyositis (CADM) and hypomyopathic dermatomyositis (HDM) are rare forms of DM in which skin manifestations are present with no and minimal clinical and laboratory evidence of myositis respectively. A common complication of CADM/HDM is interstitial lung disease (ILD), with the most common histopathologic variant of non-specific interstitial pneumonia (NSIP). This case highlights the development of ILD and severe muscle weakness, including proximal limb muscles, muscles of respiration and muscles of deglutition in a patient with previous diagnosis of hypomyopathic dermatomyositis.

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“…Combinatorial regulation of PD-L1 and MHC-1 expression with both CRISPR-Cas9 and CRISPR-dCas9 systems could be an effective strategy to remodel tumor immunogenicity for efficient cancer immunotherapy. However, PD-L1 and MHC-1 are also expressed in immune cells and normal tissues, , which may raise safety concerns after the systemic administration of CRISPR agents. Besides, the intrinsic mechanism of the CRISPR system requires that it must overcome multiple physiological barriers to enter targeted cells .…”

mentioning

confidence: 99%

Remodeling Tumor Immunogenicity with Dual-Activatable Binary CRISPR Nanomedicine for Cancer Immunotherapy

et al. 2023

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The specific recognition of cancer cells by the body's immune system is an essential step in initiating antitumor immunity. However, the decreased expression of major histocompatibility complex class I (MHC-1) and overexpression of programmed death ligand 1 (PD-L1) causes insufficient tumor-associated antigens presentation and inactivation of T cells, which accounts for poor immunogenicity. To remodel tumor immunogenicity, herein, a dual-activatable binary CRISPR nanomedicine (DBCN) that can efficiently deliver a CRISPR system into tumor tissues and specifically control its activation is reported. This DBCN is made of a thioketal-cross-linked polyplex core and an acid-detachable polymer shell, which can maintain stability during blood circulation, while detaching a polymer shell to facilitate the cellular internalization of the CRISPR system after entering tumor tissues and ultimately activating gene editing under exogenous laser irradiation, thereby maximizing the therapeutic benefits and reducing potential safety concerns. With the collaborative application of multiple CRISPR systems, DBCN efficiently corrects both dysregulation of MHC-1 and PD-L1 expression in tumors, thus initiating robust T celldependent antitumor immune responses to inhibit malignant tumor growth, metastasis, and recurrence. Given the increasing abundance of CRISPR toolkits, this research provides an appealing therapeutic strategy and a universal delivery platform to develop more advanced CRISPR-based cancer treatments.

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Histopathologic Findings in 5 Patients With Hypomyopathic Dermatomyositis

Cited by 6 publications

References 14 publications

NLRP3 inflammasome up-regulates major histocompatibility complex class I expression and promotes inflammatory infiltration in polymyositis

NLRP3 inflammasome up-regulates major histocompatibility complex class I expression and promotes inflammatory infiltration in polymyositis

A case of Hypomyopathic Dermatomyositis which subsequently developed to overt Myositis with ILD

Remodeling Tumor Immunogenicity with Dual-Activatable Binary CRISPR Nanomedicine for Cancer Immunotherapy

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