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  • 1
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    Online Resource
    Expansion of circulating peripheral TIGIT+CD226+ CD4 T cells with enhanced effector functions in dermatomyositis
    Springer Science and Business Media LLC ; 2021
    In:  Arthritis Research & Therapy Vol. 23, No. 1 ( 2021-12)
    Details
    In: Arthritis Research & Therapy, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2021-12)
    Abstract: T cell Ig and ITIM domain (TIGIT)/CD226 pathway has a critical role in regulating T cell responses and has come to the forefront in cancer as a promising immunotherapeutic target. However, its role in autoimmune diseases is just beginning to be elucidated. Dermatomyositis (DM) is an autoimmune disease, in which T cell dysregulation plays a pivotal role, and importantly, it is a common immune-related adverse event in response to treatment of cancers with immune checkpoint inhibitors, but no studies have implicated the TIGIT/CD226 axis in DM. Methods We recruited 30 treatment-naïve DM patients and 26 healthy controls. Flow cytometry analysis was used to investigate the co-expression of TIGIT and CD226 on T cells in blood samples. Magnetic bead or FACS-based cell isolation, T cell proliferation assay, and intracellular cytokine staining were performed to analyze the functions of different TIGIT/CD226 phenotypes. Recombinant proteins CD155, CD112, and anti-CD226 antibodies were used to suppress the function of TIGIT/CD226-expressing CD4 T cells. Results Four distinct subsets of T cells based on TIGIT/CD226 co-expression, TIGIT+CD226−, TIGIT+CD226+, TIGIT−CD226+, and TIGIT−CD226−, were identified and characterized in DM patients. Our data showed that the function of CD4 T cell subset varied by the TIGIT/CD226 phenotype. An elevated TIGIT+CD226+ CD4 subset with enhanced effector function was observed in patients with DM, especially the patients complicated with interstitial lung disease. This subpopulation was closely related to DM activity and decreased significantly in DM remission after treatment. Furthermore, the effector function of TIGIT+CD226+ CD4 subset could be suppressed by blocking CD226. Conclusion Our data revealed that the TIGIT and CD226 expression profiles could be used to identify functionally distinct subsets of CD4 T cells and TIGIT+CD226+ CD4 T cells is a significant subset in DM with enhanced frequency and effector function. This abnormal subset could be suppressed by blocking CD226, providing insight into the therapeutic target of the TIGIT/CD226 axis.
    Type of Medium: Online Resource
    ISSN: 1478-6362
    URL: Article
    DOI: 10.1186/s13075-020-02397-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041668-4
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  • 2
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    Identification of multiple cancer-associated myositis-specific autoantibodies in idiopathic inflammatory myopathies: a large longitudinal cohort study
    Springer Science and Business Media LLC ; 2017
    In:  Arthritis Research & Therapy Vol. 19, No. 1 ( 2017-12)
    Details
    In: Arthritis Research & Therapy, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2017-12)
    Type of Medium: Online Resource
    ISSN: 1478-6362
    URL: Article
    DOI: 10.1186/s13075-017-1469-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2041668-4
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  • 3
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    DataSheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 12 ( 2022-1-5)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-5)
    Abstract: Immune-mediated necrotizing myopathy (IMNM) is characterized by manifestation of myonecrosis and regeneration of muscle fibers; however, the underlying pathogenesis remains unclear. This study aimed to investigate the role and mechanism of miR-18a-3p and its target RNA-binding protein HuR in IMNM. HuR and miR-18a-3p levels were detected in the skeletal muscles of 18 patients with IMNM using quantitative reverse-transcription real-time polymerase chain reaction (qRT-PCR) and western blotting analysis. Human myoblasts were transfected with small interfering RNA targeting HuR and miR-18a-3p mimic or inhibitor. Myogenic differentiation markers, myogenin and myosin heavy chain, were analyzed by qRT-PCR, western blotting analysis, and immunofluorescence staining. The results showed that miR-18a-3p was upregulated (p=0.0002), whereas HuR was downregulated (p=0.002) in the skeletal muscles of patients with IMNM. The expression of miR-18a-3p in patients with IMNM was negatively correlated with those of HuR (r = -0.512, p = 0.029). We also found that disease activity was positively correlated with HuR expression ( r = 0.576, p = 0.012) but muscle activity was negatively correlated with miR-18a-3p expression ( r = -0.550, p = 0.017). Besides, bioinformatics analysis and dual-luciferase reporter assays suggested that miR-18a-3p could directly target HuR. Cellular experiments showed that overexpression of miR-18a-3p inhibited myogenic differentiation by targeting HuR, whereas inhibition of miR-18a-3p led to opposite results. Therefore, miR-18a-3p and its target protein HuR may be responsible for modulating the myogenic process in IMNM and can thus be therapeutic targets for the same.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.780237
    DOI: 10.3389/fimmu.2021.780237.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 4
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    Different Multivariable Risk Factors for Rapid Progressive Interstitial Lung Disease in Anti-MDA5 Positive Dermatomyositis and Anti-Synthetase Syndrome
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-3-7)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-3-7)
    Abstract: Interstitial lung disease (ILD) is frequently observed in anti-melanoma differentiation-associated protein 5 (MDA5) antibody positive dermatomyositis (DM) and anti-synthetase syndrome (ASS), where they often develop a rapidly progressive ILD (RP-ILD) leading to poor prognosis. Objective The aim of this study was to construct multivariable prediction risk factors for rapid progressive ILD (RP-ILD) in anti-MDA5 positive DM (MDA5 + DM) and ASS. Methods 333 idiopathic inflammatory myopathy (IIM) associated ILD patients were studied retrospectively. Risk factors for RP-ILD in MDA5 + DM and ASS patients were identified by univariate and multivariable logistic regression analysis. The mortality was assessed using Kaplan-Meier analysis. Results RP-ILD was more prevalent in MDA5 + DM patients than ASS patients. MDA5 + DM patients with RP-ILD had significantly lower survival rates than those in ASS patients. The independent risk factors for RP-ILD in MDA5 + DM patients were fever (OR 3.67, 95% CI:1.79-7.52), lymphopenia (OR 2.14, 95% CI:1.01-4.53), especially decreased levels of CD3 + T cells (OR 2.56, 95% CI:1.17-5.61), decreased levels of CD3 + CD4 + T cells (OR 2.80, 95% CI:1.37-5.73), CD3 + CD8 + T cells (OR 2.18, 95% CI:1.05-4.50), elevated CD5 - CD19 + B cells (OR 3.17, 95% CI:1.41-7.13), elevated ALT (OR 2.36, 95% CI:1.15-4.81), high lactate dehydrogenase (LDH) (OR 3.08, 95% CI:1.52-6.27), hyper-ferritin (OR 4.97, 95% CI:1.97-12.50), elevated CEA (OR 2.28, 95% CI:1.13-4.59), and elevated CA153 (OR 3.31, 95% CI:1.50-7.27). While the independent risk factors for RP-ILD in ASS patients were elevated CEA (OR 5.25, 95% CI: 1.73-15.93), CA125 (OR 2.79, 95% CI: 1.10-7.11) and NSE (OR 4.86, 95% CI: 1.44-16.37). Importantly, serum ferritin & gt;2200ng/ml predicted patient’s death within half a year in MDA5 + DM patients with RP-ILD, but not in ASS patients. Conclusions There were significant different mortality and multivariable risk factors for RP-ILD in MDA5 + DM patients and ASS patients. Potential clinical benefits of using these different risk factors deserve assessment of severity and prognosis in IIM patients.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.845988
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 5
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    Interstitial Lung Disease Is a Major Characteristic of Patients Who Test Positive for Anti-PM/Scl Antibody
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 8 ( 2022-1-18)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2022-1-18)
    Abstract: This study aimed to analyze the clinical features of anti-PM/Scl antibodies in Chinese patients. Method We reviewed the clinical data of anti-PM/Scl antibody-positive patients, including their long-term follow-up. Results A total of 30 patients carried anti-PM/Scl antibodies, 21 (70%) were females, and the mean age was 55.4 years, 15 (50%) and 10 (33.3%) patients were positive for anti-PM/Scl-75 and anti-PM/Scl-100, respectively. Fifteen cases (50%) were diagnosed as inflammatory myopathy, namely, 11 dermatomyositis (DM) and 4 polymyositis (PM). Five (16.7%) patients were diagnosed with overlap syndrome, and only one (3.3%) was diagnosed as systemic sclerosis. The other 9 (30%) patients were classified as undifferentiated connective tissue disease. Twenty-six (86.7%) had interstitial lung disease (ILD) and was the sole manifestation in 8 (26.7%) patients, 15 (58.0%) showed non-specific interstitial pneumonia based on high-resolution CT or lung biopsy. The majority of patients (95%) with mild and moderate groups on basis of pulmonary function tests. Compared to the anti-PM/Scl-100 group, the occurrence of clinical characteristics was not significantly different from the anti-PM/Scl-75 group, except the levels of C-reactive protein and erythrocyte sedimentation rate in the anti-PM/Scl-75 antibody-positive group were higher ( p & lt; 0.05). All patients with positive Ro-52 antibodies had ILD and were more likely to develop skin rash in the group with Ro-52 ( p = 0.024). With a follow-up of the present cohort, 70.8% improved with treatment, but 16.7% of patients are easy to relapse. Conclusion The anti-PM/Scl antibody occurred frequently in DM/PM patients, ILD was the major clinical feature, especially in patients combined with Ro-52. Some patients may complicate with ILD alone without extrapulmonary manifestations. Anti-PM/Scl antibodies positive patients were responsive to treatment.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2021.778211
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 6
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    Clinical characteristics of anti-SAE antibodies in Chinese patients with dermatomyositis in comparison with different patient cohorts
    Springer Science and Business Media LLC ; 2017
    In:  Scientific Reports Vol. 7, No. 1 ( 2017-03-15)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-03-15)
    Abstract: This study aimed to analyze the clinical features of anti-SAE antibodies in Chinese myositis patients in comparison with different cohorts. The anti-SAE antibodies were tested in myositis patients and in control subjects. Long-term follow-up was conducted on the antibody-positive patients. Anti-SAE antibodies were exclusively present in 12 out of 394 (3.0%) adult dermatomyositis (DM) patients. Of the anti-SAE-positive DM patients, 75% had distinctive diffuse dark-red or pigment-like skin rashes, and 67% of these patients experienced mild muscle weakness. Muscular biopsies showed mild pathological manifestations. Compared with the antibody-negative group, the average age of dermatomyositis onset in the antibody-positive group was higher, and dysphagia occurred more frequently noted ( p  = 0.012). Only 9 patients received follow-up, 7 experienced improvement after treatment. The anti-SAE antibody levels correlated with improved disease condition. The anti-SAE antibody was found exclusively in adult DM patients, occurring infrequently in Chinese patients. In addition to a diffuse dark-red or pigment-like skin rash and mild muscular weakness, common symptoms included propensity for developing dysphagia. Serum levels of the anti-SAE antibody correlated with myositis disease activity, and anti-SAE-positive patients were responsive to treatment.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-017-00240-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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  • 7
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    High prevalence and mortality of Pneumocystis jirovecii pneumonia in anti-MDA5 antibody-positive dermatomyositis
    Oxford University Press (OUP) ; 2023
    In:  Rheumatology Vol. 62, No. 10 ( 2023-10-03), p. 3302-3309
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. 10 ( 2023-10-03), p. 3302-3309
    Abstract: To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5+ DM) patients, and to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS). Methods Anti-MDA5+ DM patients who underwent mNGS or real-time PCR for PJP detection were recruited. The potential risk factors for PJP occurrence and death were analysed via Logistic regression and Cox proportional hazards regression, respectively. The diagnostic efficacy of mNGS was compared with the conventional methods. Results 91 patients were enrolled and 44 were assigned to PJP+ group. The PJP detection rate was 48.4%. PJP often occurred in the first 3 months (68.2%) of the disease; this period also showed the highest mortality rate (20.5%). Fever and increased lactate dehydrogenase (LDH) were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all P  & lt; 0.05). Older age and increased LDH were predictors for mortality in patients with anti-MDA5+ DM and PJP (all P  & lt; 0.05). In addition, we found that mNGS had a sensitivity of 100.0% and specificity of 90.0% in diagnosing PJP, with the highest area under the curve of 0.95 (P  & lt; 0.001). Conclusion PJP has high prevalence and mortality in anti-MDA5+ DM. It is crucial for clinicians to identify high-risk patients and promptly institute TMP/SMZ to prevent PJP. mNGS is the preferred approach for pathogen detection in anti-MDA5+ DM when PJP is suspected.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/kead063
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474143-X
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  • 8
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    Significant decrease in peripheral regulatory B cells is an immunopathogenic feature of dermatomyositis
    Springer Science and Business Media LLC ; 2016
    In:  Scientific Reports Vol. 6, No. 1 ( 2016-06-07)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-06-07)
    Abstract: Regulatory B cells (Bregs) are critical in maintaining self-tolerance. Their role in dermatomyositis (DM), an autoimmune disease characterized by inappropriate regulation of hyperactivated B and T cells, has not been clearly defined. In the current study, we performed flow cytometry analysis of studied CD19 + CD24 high CD38 high Breg subpopulations in blood samples from 30 patients with DM, 37 diseased controls and 23 healthy controls. A significant decrease was observed in the frequency of Bregs in DM patients compared to that in diseased controls ( p   〈  0.0001) and in healthy controls ( p   〈  0.0001). And the prevalence of Bregs deficiency (defined as Bregs/B cells  〈  0.50% in this study) in DM patients went as high as 73.3%. Furthermore, DM patients with positive myositis specific autoantibody often had lower Bregs levels than negative patients ( p  = 0.036) and lower level of Bregs was also found in DM patients with interstitial lung disease than in DM patients without ( p  = 0.041). In a follow-up study, seven DM patients were considered to be in remission stage and their Breg levels were found to have significantly increased after treatment ( p  = 0.022). Our research revealed that Breg deficiency is an immunopathogenic feature of DM and provided insights into the design of new immunotherapy target for DM clinical interventions.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/srep27479
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2615211-3
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  • 9
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    HMGB1 May Be a Biomarker for Predicting the Outcome in Patients with Polymyositis /Dermatomyositis with Interstitial Lung Disease
    Public Library of Science (PLoS) ; 2016
    In:  PLOS ONE Vol. 11, No. 8 ( 2016-8-18), p. e0161436-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 11, No. 8 ( 2016-8-18), p. e0161436-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1371/journal.pone.0161436
    DOI: 10.1371/journal.pone.0161436.g001
    DOI: 10.1371/journal.pone.0161436.g002
    DOI: 10.1371/journal.pone.0161436.g003
    DOI: 10.1371/journal.pone.0161436.t001
    DOI: 10.1371/journal.pone.0161436.t002
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2016
    detail.hit.zdb_id: 2267670-3
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  • 10
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    Peripheral lymphocyte count defines the clinical phenotypes and prognosis in patients with anti‐MDA5‐positive dermatomyositis
    Wiley ; 2023
    In:  Journal of Internal Medicine Vol. 293, No. 4 ( 2023-04), p. 494-507
    Details
    In: Journal of Internal Medicine, Wiley, Vol. 293, No. 4 ( 2023-04), p. 494-507
    Abstract: To explore the role of peripheral lymphocyte count in phenotyping and prognosis prediction in dermatomyositis (DM) patients with anti‐MDA5 antibodies. Methods In total, 1669 patients with idiopathic inflammatory myopathy (IIM) were retrospectively enrolled. Clinical characteristics and prognosis of patients with anti‐MDA5+ DM were analyzed in association with peripheral lymphocyte counts and clusters determined by unsupervised machine learning. Results The peripheral lymphocyte count was significantly lower in the anti‐MDA5+ DM group ( N  = 421) than in the other IIM serotype groups. The anti‐MDA5+ DM patients were divided into three groups; the severe lymphopenia group had skin ulcers and rapidly progressive interstitial lung disease (RP‐ILD); patients with a normal lymphocyte count had a younger age of onset, more frequent arthritis, and normal serum ferritin levels, whereas mild lymphopenia group showed a moderate increase of serum ferritin and intermediate incidence of RP‐ILD. Survival analysis revealed that the 3‐ and 6‐month mortality rates were significantly higher in the severe lymphopenia group (29.0% and 42.1%, respectively) than in the mild lymphopenia group and normal lymphocyte count group ( p value 〈 0.001). Consistently, unsupervised machine learning identified three similar groups; the arthritis cluster shows the highest lymphocyte counts and best prognosis; the RP‐ILD cluster presents the lowest peripheral lymphocyte, high incidence of RP‐ILD, and poor prognosis; the typical DM rash cluster had a moderate peripheral lymphocyte count and an intermediate prognosis. Conclusions Lymphopenia is a unique manifestation of anti‐MDA5+ DM. Peripheral lymphocyte count can define clinical phenotypes and predict prognosis in anti‐MDA5+ DM.
    Type of Medium: Online Resource
    ISSN: 0954-6820 , 1365-2796
    URL: Issue
    URL: Article
    DOI: 10.1111/joim.v293.4
    DOI: 10.1111/joim.13607
    RVK:
    XA 54380
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2006883-9
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