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  • 1
    Online Resource
    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
    Online Resource
    Online Resource
    The RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositis
    Springer Science and Business Media LLC ; 2019
    In:  Arthritis Research & Therapy Vol. 21, No. 1 ( 2019-12)
    Details
    In: Arthritis Research & Therapy, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2019-12)
    Type of Medium: Online Resource
    ISSN: 1478-6362
    URL: Article
    DOI: 10.1186/s13075-019-1905-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2041668-4
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  • 3
    Online Resource
    Online Resource
    Efficacy and Safety of Tofacitinib in Anti–Melanoma Differentiation–Associated 5 Gene Antibody–Positive Dermatomyositis
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  JCR: Journal of Clinical Rheumatology Vol. 29, No. 6 ( 2023-9), p. 281-284
    Details
    In: JCR: Journal of Clinical Rheumatology, Ovid Technologies (Wolters Kluwer Health), Vol. 29, No. 6 ( 2023-9), p. 281-284
    Abstract: This study aimed to evaluate the efficacy and safety of tofacitinib for the treatment of anti–melanoma differentiation–associated 5 gene (anti-MDA5) antibody–positive dermatomyositis (DM). Methods This study included 52 patients with anti-MDA5 antibody–positive DM (MDA5 + DM) who were treated with tofacitinib and followed up. Clinical and laboratory data of these patients were recorded between January 2019 and June 2022. SPSS was used for all statistical analyses. Results The mean age of patients with MDA5 + DM was 45 ± 12.4 years, and the median disease duration was 6.5 months (range, 3–13 months). The mean dosage of glucocorticoids was 34.7 ± 20.9 mg/d at the initiation of tofacitinib therapy. Overall, 47 patients were followed up for a mean duration of 7.8 ± 6.2 months. We found that the clinical symptoms of 28 patients (59.6%) were improved, but 1 patient (2.1%) died because of severe infection. Moreover, complications occurred in 25 patients (53.2%), among whom 19 patients had infections. Older age and C-reactive protein levels close to the upper value in reference range at the initial treatment were found to be the potential risk factors of infection. Furthermore, patients with cutaneous ulcers were found to have a lower risk of infection. Conclusion Tofacitinib can be used as a potential therapeutic option for MDA5 + DM. The occurrence of infection requires special attention during treatment, particularly in patients with older age and C-reactive protein levels close to the upper value in reference range.
    Type of Medium: Online Resource
    ISSN: 1536-7355 , 1076-1608
    URL: Article
    DOI: 10.1097/RHU.0000000000002010
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2071025-2
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  • 4
    Online Resource
    Online Resource
    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-8-30)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-8-30)
    Abstract: To explore the clinical features and prognoses of dermatomyositis (DM) associated with a double-positive anti-MDA5 and anti-aminoacyl-tRNA synthetase (anti-ARS) antibody presentation. Methods We retrospectively analyzed 1280 consecutive patients with idiopathic inflammatory myopathy (IIM). Individuals with anti-MDA5 and anti-ARS antibodies (anti-MDA5+/ARS+) were compared to anti-MDA5-/ARS+ and anti-MDA5+/ARS- control individuals based on clinical, pulmonary radiological characteristics, treatment, and follow-up information. Results Six individuals (0.47%) presented with anti-MDA5+/ARS+; of these, 2 (33.3%) were anti-PL-12+, 2 (33.3%) were anti-Jo-1+, 1 (16.7%) was anti-EJ+, and 1 (16.7%) was anti-PL-7+. Hallmark cutaneous manifestations, including Gottron’s sign (100%), heliotrope rash (50%), mechanic’s hand (66.7%), and skin ulcers (16.7%) were common. Anti-MDA5+/ARS+ patients tended to have higher ferritin levels (p = 0.038) than anti-MDA5-/ARS+ group, and higher CD4+ T-cell counts (p = 0.032) compared to the anti-MDA5+/ARS- group. Radiologically, NSIP with OP overlap was predominant (60%). Consolidation (60%), ground-glass attenuation (GGA) (80%), traction bronchiectasis (80%), and intralobular reticulation (100%) were common in anti-MDA5+/ARS+ individuals. All were diagnosed with ILD and 50% were categorized as RPILD. All patients received glucocorticoids combined with one or more immunosuppressants. Most (83.3%) had a good prognosis following treatment, but there was no difference in the survival rate between the three subgroups. Conclusion Presentation with anti-MDA5+/ARS+ DM was rare. The clinical and radiological characteristics of anti-MDA5+/ARS+ DM combined the features of anti-MDA5+ and anti-ARS+ individuals. Individuals with anti-MDA5+/ARS+ antibodies may respond well to glucocorticoid therapy; glucocorticoids combined with one or more immunosuppressants may be considered a basic treatment approach.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.987841
    DOI: 10.3389/fimmu.2022.987841.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 5
    Online Resource
    Online Resource
    Muscle pathological features and extra-muscle involvement in idiopathic inflammatory myopathies with anti-mitochondrial antibody
    Elsevier BV ; 2021
    In:  Seminars in Arthritis and Rheumatism Vol. 51, No. 4 ( 2021-08), p. 741-748
    Details
    In: Seminars in Arthritis and Rheumatism, Elsevier BV, Vol. 51, No. 4 ( 2021-08), p. 741-748
    Type of Medium: Online Resource
    ISSN: 0049-0172
    URL: Article
    DOI: 10.1016/j.semarthrit.2021.05.019
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2048942-0
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  • 6
    Online Resource
    Online Resource
    Clinical, radiological and pathological features of anti-MDA5 antibody-associated interstitial lung disease
    BMJ ; 2023
    In:  RMD Open Vol. 9, No. 2 ( 2023-05), p. e003150-
    Details
    In: RMD Open, BMJ, Vol. 9, No. 2 ( 2023-05), p. e003150-
    Abstract: To investigate the clinical, radiographic and pathological features of interstitial lung disease (ILD) in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5+DM). Methods We retrospectively analysed the medical records of patients with anti-MDA5+DM who had undergone radiological examination, and lung histopathology was performed on 17 of them. Results This study examined 329 patients with anti-MDA5+DM, of whom 308 (93.6%) were diagnosed with ILD and 177 (53.8%) exhibited rapidly progressive ILD (RPILD). The most common radiographic patterns were organising pneumonia (OP) (43.2%), non-specific interstitial pneumonia (NSIP) (26.4%) and NSIP+OP (18.5%). Histological analysis showed NSIP (41.2%) and NSIP+OP (47.1%) to be the predominant patterns. However, in the 17 patients who underwent lung histopathology, the coincidence rate between radiological and histopathological diagnoses was only 11.8%. Compared with patients without RPILD, those with RPILD showed a higher prevalence of NSIP+OP (26.6% vs 10.7%, p=0.001) and a lower prevalence of NSIP pattern (21.5% vs 37.4%, p=0.002) on high-resolution CT. Furthermore, patients with radiographic patterns of NSIP+OP or diffuse alveolar damage (DAD) had more risk factors for poor prognosis, with 12-month mortality rates of 45.9% and 100%, respectively. Conclusions RPILD was commonly observed in patients with anti-MDA5+DM. OP was identified as the predominant radiographic pattern, which corresponded to a histopathological pattern of NSIP or NSIP+OP. Notably, patients exhibiting radiographic patterns of NSIP+OP or DAD were shown to have a poor prognosis.
    Type of Medium: Online Resource
    ISSN: 2056-5933
    URL: Article
    DOI: 10.1136/rmdopen-2023-003150
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2812592-7
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  • 7
    Online Resource
    Online Resource
    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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  • 8
    Online Resource
    Online Resource
    Cyclophosphamide treatment for idiopathic inflammatory myopathies and related interstitial lung disease: a systematic review
    Springer Science and Business Media LLC ; 2015
    In:  Clinical Rheumatology Vol. 34, No. 1 ( 2015-1), p. 99-105
    Details
    In: Clinical Rheumatology, Springer Science and Business Media LLC, Vol. 34, No. 1 ( 2015-1), p. 99-105
    Type of Medium: Online Resource
    ISSN: 0770-3198 , 1434-9949
    URL: Article
    DOI: 10.1007/s10067-014-2803-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 1480901-1
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  • 9
    Online Resource
    Online Resource
    The efficacy of tacrolimus in patients with refractory dermatomyositis/polymyositis: a systematic review
    Springer Science and Business Media LLC ; 2015
    In:  Clinical Rheumatology Vol. 34, No. 12 ( 2015-12), p. 2097-2103
    Details
    In: Clinical Rheumatology, Springer Science and Business Media LLC, Vol. 34, No. 12 ( 2015-12), p. 2097-2103
    Type of Medium: Online Resource
    ISSN: 0770-3198 , 1434-9949
    URL: Article
    DOI: 10.1007/s10067-015-3065-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 1480901-1
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  • 10
    Online Resource
    Online Resource
    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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