IFN-γ: An overlooked cytokine in dermatomyositis with anti-MDA5 antibodies

Thuner, Jonathan; Coutant, Frédéric

doi:10.1016/j.autrev.2023.103420

Cited by 10 publications

(3 citation statements)

References 90 publications

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“…The probability of anti-MDA5 antibody positivity in ulcerative Gottron's sign was generally higher than that in the no-ulcer group, and only 3-19% of DM patients would develop skin ulcers with severe pain, and even face the risk of disability at a later stage. 12,13 In this case, the necrosis of the skin ulcer may even invade the bone layer, which is rare. It is now believed that this disease is mainly caused by type I interferon (IFN), and the expression of serum IFN-α is increased in patients with anti-MDA5-positive dermatomyositis.…”

Section: Discussionmentioning

confidence: 91%

A Case of Dermatomyositis with Coexistence of Positive Anti-MDA5 Antibodies and Anti-SSA/RO52 Antibodies, Combined with Necrotic Skin Ulcers

Sun,

Hu,

et al. 2024

IMCRJ

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Background Dermatomyositis (DM) is an idiopathic inflammatory myopathy that is clinically challenging to diagnose and has a poor prognosis. It is characterized by symmetric proximal muscle weakness, muscle tenderness, dysphagia, characteristic skin rash (heliotrope rash, Gottron’s sign), elevated muscle enzyme levels, abnormal electromyography, and muscle biopsy findings. DM with positive anti-MDA5 antibodies is mainly characterized by Gottron’s sign, skin ulcers, facial erythema, mechanic’s hands, and V-sign. In this case, the patient presented with the rare manifestation of severe necrotic skin ulcers in association with Gottron’s sign, prompting us to report this case. Case Presentation A 45-year-old female was admitted to the hospital with systemic joint pain, fatigue, multiple ulcers, and purulent discharge on both hands. Her myositis-specific antibody profile revealed positive anti-MDA5 and anti-SSA/RO52 antibodies. Treatment included a combination of glucocorticoids, immunosuppressants, gastric and liver protection, infection control, and wound care. After two weeks of treatment, the patient showed improvement in symptoms. However, on the 24th day of hospitalization, the wound at the right elbow joint ruptured and became infected, requiring debridement and skin grafting in the appropriate department. Conclusion There has been limited research and reported cases of dermatomyositis with coexistence of positive anti-MDA5 and anti-SSA/RO52 antibodies combined with severe skin ulcers. Therefore, we present this rare case and emphasize the need for close follow-up on pulmonary involvement and skin ulcer progression, as well as timely implementation of new treatment strategies to actively improve the prognosis.

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Section: Discussionmentioning

confidence: 91%

A Case of Dermatomyositis with Coexistence of Positive Anti-MDA5 Antibodies and Anti-SSA/RO52 Antibodies, Combined with Necrotic Skin Ulcers

Sun,

Hu,

et al. 2024

IMCRJ

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“…One hypothesis is that the depletion of circulating NK cells may be due to their migration from the peripheral circulation to the local site or apoptosis, reported by related clinical studies about ASS ( 26 ), SSc ( 40 , 41 ), and sarcoidosis ( 42 ). Notably, the migration of NK cells to the lungs in anti-MDA5 + DM patients may be driven by the local production of chemokines induced by IFN-γ, such as CXCL10 ( 43 , 44 ). Once recruited to the lungs, NK cells can further secrete IFN-γ, creating a positive feedback loop that amplifies the inflammatory response and exacerbates tissue damage ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies

Shao,

Xia,

Zhen

et al. 2024

Front. Immunol.

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ObjectivesInterstitial lung disease (ILD) is one of the common extramuscular involvement in idiopathic inflammatory myopathies (IIMs) (1). Several patients develop a progressive fibrosing ILD (PF-ILD) despite conventional treatment, resulting in a progressive deterioration in their quality of life (2). Here, we investigated the clinical and immune characteristics of IIM-ILD and risk factors for PF-ILD in IIM, mainly in anti-melanoma differentiation-associated protein 5 (anti-MDA5+) dermatomyositis (DM) and anti-synthetase syndrome (ASS).MethodsHere, a prospective cohort of 156 patients with IIM-ILD were included in the longitudinal analysis and divided into the PF-ILD (n=65) and non-PF-ILD (n=91) groups, and their baseline clinical characteristics were compared. Univariate and multivariate Cox analyses were performed to identify the variables significantly associated with pulmonary fibrosis progression in the total cohort, then anti-MDA5+ DM and ASS groups separately.ResultsPeripheral blood lymphocyte counts, including T, B, and NK cell counts, were significantly lower in the PF-ILD group than in the non-PF-ILD group. This characteristic is also present in the comparison between patients with anti-MDA5+ DM and ASS. The multivariate Cox regression analysis revealed that age > 43.5 years [HR: 7.653 (95% CI: 2.005-29.204), p = 0.003], absolute NK cell count < 148 cells/μL [HR: 6.277 (95% CI: 1.572-25.067), p = 0.009] and absolute Th cell count < 533.2 cells/μL [HR: 4.703 (95% CI: 1.014-21.821), p = 0.048] were independent predictors of progressive fibrosing during 1-year follow-up for patients with anti-MDA5+ DM, while absolute count of NK cells < 303.3 cells/µL [HR: 19.962 (95% CI: 3.108-128.223), p = 0.002], absolute count of lymphocytes < 1.545×109/L [HR: 9.684 (95% CI: 1.063-88.186), p = 0.044], and ferritin > 259.45 ng/mL [HR: 6 (95% CI: 1.116-32.256), p = 0.037] were independent predictors of PF-ILD for patients with ASS.ConclusionsPatients with anti-MDA5+ DM and ASS have independent risk factors for PF-ILD. Lymphocyte depletion (particularly NK cells) was significantly associated with PF-ILD within 1-year of follow-up for IIM-ILD

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“…Therefore, it is essential to undertake comprehensive studies in the future to elucidate this relationship. IFN-γ is the sole member of type II interferons and is produced not only by T cells, macrophages, and NK cells but also by thyroid cells ( 39 ). Its immunomodulatory effects include increased phagocytosis of macrophages, NK cell activation, enhancing the expression level of its antigens, and the toxicity of sensitized lymphocytes on target cells ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

Causal relationship between inflammatory cytokines and autoimmune thyroid disease: a bidirectional two-sample Mendelian randomization analysis

Yao,

Guo,

Tan

et al. 2024

Front. Immunol.

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BackgroundAutoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive.MethodsA two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves’ disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers.ResultsSeven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor–β and low levels of stem cell growth factor–β were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein–1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein–1β, MCP-1, monokine induced by interferon-γ (MIG), interferon γ–induced protein 10 (IP-10), stromal cell–derived factor–1α, platelet-derived growth factor BB, β–nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels.ConclusionOur bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.

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IFN-γ: An overlooked cytokine in dermatomyositis with anti-MDA5 antibodies

Cited by 10 publications

References 90 publications

A Case of Dermatomyositis with Coexistence of Positive Anti-MDA5 Antibodies and Anti-SSA/RO52 Antibodies, Combined with Necrotic Skin Ulcers

A Case of Dermatomyositis with Coexistence of Positive Anti-MDA5 Antibodies and Anti-SSA/RO52 Antibodies, Combined with Necrotic Skin Ulcers

Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies

Causal relationship between inflammatory cytokines and autoimmune thyroid disease: a bidirectional two-sample Mendelian randomization analysis

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