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Cutaneous and Systemic Findings Associated With Nuclear Matrix Protein 2 Antibodies in Adult Dermatomyositis Patients.

ABSTRACT: To characterize the cutaneous and systemic clinical phenotype of dermatomyositis patients with antinuclear matrix protein 2 (anti-NXP-2) antibodies.We conducted a retrospective cohort analysis of 178 dermatomyositis patients seen at the Stanford University Clinic. An electronic chart review employing a keyword search strategy was performed to collect clinical and laboratory data. Anti-NXP-2 antibodies were assayed by immunoprecipitation using NXP-2 produced by in vitro transcription/translation.Antibodies to NXP-2 were detected in 20 of the 178 patients (11%). Anti-NXP-2 antibodies were associated with male sex (50% versus 25%; P = 0.02), dysphagia (74% versus 39%; P = 0.006), myalgia (89% versus 52%; P = 0.002), peripheral edema (35% versus 11%; P = 0.016), and calcinosis (37% versus 11%; P = 0.007). These patients were less likely to be clinically amyopathic (5% versus 23%; P = 0.08). Five of the 20 patients with anti-NXP-2 antibodies (25%) had an associated internal malignancy. No other cutaneous characteristics were associated with anti-NXP-2 antibodies, except a decreased frequency of Gottron's sign (44% versus 75%; P = 0.012) and a greater likelihood of having mild skin disease.Dermatomyositis patients with anti-NXP-2 antibodies have a distinct and often severe systemic phenotype that includes myalgia, peripheral edema, and significant dysphagia, despite having milder inflammatory skin disease.

SUBMITTER: Rogers A

PROVIDER: S-EPMC5529261 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Cutaneous and Systemic Findings Associated With Nuclear Matrix Protein 2 Antibodies in Adult Dermatomyositis Patients.

Rogers Anna A Chung Lorinda L Li Shufeng S Casciola-Rosen Livia L Fiorentino David F DF

Arthritis care & research 20171102 12

<h4>Objective</h4>To characterize the cutaneous and systemic clinical phenotype of dermatomyositis patients with antinuclear matrix protein 2 (anti-NXP-2) antibodies.<h4>Methods</h4>We conducted a retrospective cohort analysis of 178 dermatomyositis patients seen at the Stanford University Clinic. An electronic chart review employing a keyword search strategy was performed to collect clinical and laboratory data. Anti-NXP-2 antibodies were assayed by immunoprecipitation using NXP-2 produced by i ...[more]

PMID: 28129490

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Project description:ImportanceReports on dermatomyositis (DM) sine dermatitis (DMSD) are scarce, and the concept of the disease has not been widely accepted.ObjectiveTo confirm the existence of DMSD, determine its prevalence, and characterize its serologic features.Design, setting, and participantsThis is a cohort study that reviewed clinical information, laboratory data, and muscle pathology slides from January 2009 to August 2019. We further assessed the follow-up data of 14 patients with DMSD. The median (interquartile range) follow-up period was 34 (16-64) months. Muscle biopsy samples, along with clinical information and laboratory data, were sent to a referral center for muscle diseases in Japan for diagnosis. Of patients whose myopathologic diagnosis was made at the National Center of Neurology and Psychiatry between January 2009 and August 2019, 199 patients were eligible for inclusion. These patients underwent full investigation for DM-specific autoantibodies (against transcriptional intermediary factor γ, Mi-2, melanoma differentiation-associated gene 5, nuclear matrix protein 2 [NXP-2], and small ubiquitin-like modifier activating enzyme ); however, 17 patients were excluded because their muscle fibers did not express myxovirus resistance protein A, a sensitive and specific marker of DM muscle pathology.Main outcomes and measuresDiagnosis of DMSD was based on the absence of a skin rash at the time of muscle biopsy.ResultsOf the 182 patients, 93 were women (51%) and 46 were children (25%) (<18 years). Fourteen patients (8%) had DMSD and none were clinically diagnosed with DM. Among the 14 patients with DMSD, 12 (86%) were positive for anti-NXP-2 autoantibodies, while the remaining 2 were positive for anti-transcriptional intermediary factor γ and anti-Mi-2 autoantibodies, respectively. Only 28% of patients (47 of 168) with a skin rash were positive for anti-NXP-2 autoantibodies, indicating a significant association between anti-NXP-2 autoantibodies and DMSD (86% [12 of 14] vs 28% [47 of 168]; P < .001). This association was also supported by multivariable models adjusted for disease duration (odds ratio, 126.47; 95% CI, 11.42-1400.64; P < .001).Conclusions and relevanceDermatomyositis sine dermatitis does exist and accounts for 8% of patients with DM confirmed with muscle biopsy. Dermatomyositis sine dermatitis is significantly associated with anti-NXP-2 autoantibodies, which contrasts with anti-MDA5 DM, which is typically clinically amyopathic in presentation. It is essential to distinguish DMSD from other types of myositis because DM-specific therapies that are currently under development, including Janus kinase inhibitors, may be effective for DMSD.

Project description:ImportanceCutaneous disease in dermatomyositis has no standardized treatment approach and so presents a challenging task for patients and clinicians.ObjectiveTo study the efficacy and safety of apremilast as an add-on therapy in patients with recalcitrant cutaneous dermatomyositis.Design, setting, and participantsThis phase 2a, open-label, single-arm nonrandomized controlled trial was conducted at a single center from June 2018 to June 2021. Participants were 8 patients with recalcitrant cutaneous dermatomyositis, defined by a cutaneous disease activity severity index (CDASI) score greater than 5 despite treatment with steroids, steroid-sparing agents, or both. Data were analyzed from June 2018 to June 2021.InterventionsApremilast 30 mg orally twice daily was added to ongoing treatment regimens.Main outcomes and measuresThe primary outcome was the overall response rate (ORR) at 3 months. Key secondary outcomes were the safety and toxicity of apremilast and the durability of response at 6 months. The CDASI, muscle score, dermatology life quality index (DLQI), and depression assessments were performed at baseline and regularly until month 7. Skin biopsies were performed at baseline and 3 months after apremilast (defined as 3 months into active apremilast therapy) and tested for gene expression profiling and immunohistochemical stains. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0.ResultsAmong 8 patients with recalcitrant cutaneous dermatomyositis (all women; mean [SD] age, 54 [15.9] years), a response was found at 3 months after apremilast among 7 patients (ORR, 87.5%). The mean (SD) decrease in CDASI was 12.9 (6.3) points at 3 months (P < .001). Apremilast was well tolerated, with no grade 3 or higher adverse events. Sequencing of RNA was performed on skin biopsies taken from 7 patients at baseline and at 3 months after therapy. Appropriate negative (ie, no primary antibody) and positive (ie, tonsil and spleen) controls were stained in parallel with each set of slides studied. Of 39 076 expressed genes, there were 195 whose expression changed 2-fold or more at P < .01 (123 downregulated and 72 upregulated genes). Gene set enrichment analysis identified 13 pathways in which apremilast was associated with downregulated expression, notably signal transducers and activators of transcription 1 (STAT1), STAT3, interleukin 4 (IL-4), IL-6, IL-12, IL-23, interferon γ (IFNγ), and tumor necrosis factor α (TNFα) pathways. In immunohistochemical staining, there was a mean (SD) decrease in phosphorylation levels STAT1 (22.3% [28.3%] positive cells) and STAT3 (13.4% [11.6%] positive cells) at the protein level, a downstream signaling pathway for the downregulated cytokines.Conclusions and relevanceThese findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways.Trial registrationClinicalTrials.gov Identifier: NCT03529955.

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Cutaneous and Systemic Findings Associated With Nuclear Matrix Protein 2 Antibodies in Adult Dermatomyositis Patients.

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Cutaneous and Systemic Findings Associated With Nuclear Matrix Protein 2 Antibodies in Adult Dermatomyositis Patients.

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