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Nasr, Rawad; Reed, Ann M.; Peterson, Erik

doi:10.1097/bor.0b013e3283585731

Cited by 11 publications

(2 citation statements)

References 47 publications

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“…For instance, the aberrant neutrophil extracellular trap (NET) formation may be involved in the pathogenesis of ILD in DM patients ( Peng et al, 2018 ), and proteinase 3, one type of neutrophil serine proteinases, is lower in patients of DM without ILD ( Gao et al, 2018 ). We also confirmed previous observations related to the pathogenesis of DM and DM-ILD, including the presence of the cytokine–cytokine receptor interaction ( Zhu et al, 2017 ; Chen et al, 2018 ), IL−17 signaling pathway ( Nasr et al, 2012 ). Additionally, we observed that complement and coagulation cascade pathway may play a critical role in DM-ILD.…”

Section: Discussionsupporting

confidence: 91%

Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease

et al. 2021

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Dermatomyositis (DM), an inflammatory disorder, is often associated with interstitial lung disease (ILD). However, the underlying mechanism remains unclear. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of differentially expressed genes (DEGs) in patients with dermatomyositis-associated interstitial lung disease (DM-ILD) and healthy controls. A total of 2,018 DEGs were identified between DM-ILD and healthy blood samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that DEGs were mainly involved in immune- and inflammatory-related biological processes and pathways. Disease ontology (DO) enrichment analysis identified 35 candidate key genes involved in both skin and lung diseases. Meanwhile, a total of 886 differentially expressed alternative splicing (AS) events were found between DM-ILD and healthy blood samples. After overlapping DEGs with differential AS genes, the plasminogen activator and urokinase receptor (PLAUR) involved in immune-related biological processes and complement and coagulation cascades was screened and identified as the most important gene associated with DM-ILD. The protein–protein interaction (PPI) network revealed that PLAUR had interactions with multiple candidate key genes. Moreover, we observed that there were significantly more neutrophils and less naive B cells in DM-ILD samples than in healthy samples. And the expression of PLAUR was significantly positively correlated with the abundance of neutrophils. Significant higher abundance of PLAUR in DM-ILD patients than healthy controls was validated by RT-qPCR. In conclusion, we identified PLAUR as an important player in regulating DM-ILD by neutrophil-associated immune response. These findings enrich our understanding, which may benefit DM-ILD patients.

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Section: Discussionsupporting

confidence: 91%

Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease

et al. 2021

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“…Pregnancy induces profound immunologic alterations that establish maternal tolerance of the semi-allogeneic fetal “graft”, but also may result in dampening of maternal protective antibody responses to infection or anti-viral vaccination [39][40]. We observed a vaccine-induced fold-increase (2.0) in influenza-specific CD4 T cells among pregnant subjects that was lower than in non-pregnant subjects (2.5 fold)[30], and at the low end of the range of vaccine-induced CD4 changes reported by others for non-pregnant healthy adults [36, 41–42].…”

Section: Discussionmentioning

confidence: 99%

Immunologic response to vaccine challenge in pregnant PTPN22 R620W carriers and non-carriers

et al. 2017

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ObjectivesInfluenza infection is a significant cause of respiratory morbidity among pregnant women. Seasonal influenza vaccination engages innate immune receptors to promote protective immunity. A coding polymorphism (R620W) in PTPN22 imparts elevated risk for human infection and autoimmune disease, predisposes to diminished innate immune responses, and associates with reduced immunization responses. We sought to quantify the effects of PTPN22-R620W on humoral and cell-mediated immune responses to the inactivated influenza vaccine among healthy pregnant women.Study DesignImmune responses were measured in healthy pregnant R620W carrier (n = 17) and non-carrier (n = 33) women receiving the 2013 quadrivalent inactivated influenza vaccine (Fluzone). Hemagglutination inhibition assays were performed to quantify neutralizing antibodies; functional influenza-reactive CD4 T cells were quantified by flow cytometry, and influenza-specific CD8 T cells were enumerated with MHC Class I tetramers. Antibody seroconversion data were evaluated by Chi-square analysis, and the Mann-Whitney or Wilcoxon signed-rank tests were applied to T cell response data.ResultsPTPN22 R620W carrier (n = 17) and non-carrier (n = 33) groups did not differ in age, parity, BMI, gestational age at time of vaccine, or history of prior influenza vaccination. After Fluzone exposure, 51.5% of non-carriers met criteria for antibody seroconversion to H1N1 influenza, compared with 23.5% of R620W carriers (p = 0.06). Influenza-reactive CD4 T cells showed modest increase at days 9–15 after vaccination in both R620W carriers and non-carriers (p = 0.02 and p = 0.04, respectively). However, there was no difference in overall response between the two groups (p = 0.6). The vaccine did not result in significant induction of influenza-specific CD8 T cells in either group.ConclusionsThere was no significant difference among healthy pregnant R620W carriers and non-carriers in H1N1 antibody seroconversion rates after influenza vaccination. Studies of larger cohorts will be needed to define the effect of PTPN22 risk allele carriage on antibody and T cell responses to influenza vaccination during pregnancy.

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Role of bone scan in the assessment of polymyositis/dermatomyositis

Suh

Jung

et al. 2014

Clin Rheumatol

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The aim of this study was to determine the significance of bone scan findings in Korean polymyositis/dermatomyositis (PM/DM) patients. The participants in this study were 26 PM/DM patients who fulfilled the proposed criteria for definite or probable PM/DM. All patients had been examined by bone scan. The results were analyzed visually and quantitatively using the uptake ratios. Correlations between the bone scan parameters of six proximal muscle groups (trapezius, deltoid, biceps, iliopsoas, quadriceps, and gluteus medius and maximus) and clinical parameters (laboratory values and manual muscle test) representing disease activities were assessed. Based on visual analyses of their bone scans, 10 of 14 (71.4 %) patients with active PM/DM had abnormal muscle uptake. Visual grading of the bone scans had a sensitivity and specificity of 74 and 90.9 %, respectively, for the assessment of muscle inflammation. Maximal proximal muscle uptake ratios, as determined on the bone scans, were significantly higher in patients with active PM/DM than in those with inactive disease (median 1.97 vs. 1.02, p = 0.046). Maximal proximal uptake ratios correlated significantly with creatine kinase (r = 0.394, p = 0.046), lactate dehydrogenase (LDH, r = 0.473, p = 0.015), aldolase (r = 0.428, p = 0.029), erythrocyte sedimentation rate (r = 0.412, p = 0.036), C-reactive protein (r = 0.454, p = 0.002), and manual muscle test results (r = -0.399, p = 0.044). Mean proximal muscle uptake ratios correlated significantly with LDH (r = 0.438, p = 0.025) and aldolase (r = 0.572, p = 0.002). Visually assessed proximal muscle uptake grades and maximal proximal muscle uptake ratios as determined by bone scan correlated significantly with the levels of known PM/DM disease activity markers. The findings of this study suggest that bone scan is a useful imaging technique for the evaluation of PM/DM patients.

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Update

Abstract: Recent advances in understanding the pathogenesis of IIM have led to discovery of molecules that are candidate biomarkers of disease activity. Type 1 interferon and myeloid-cell signatures are leading candidate markers for use in IIM activity monitoring.

Cited by 11 publications

References 47 publications

Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease

Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease

Immunologic response to vaccine challenge in pregnant PTPN22 R620W carriers and non-carriers

Role of bone scan in the assessment of polymyositis/dermatomyositis

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