Pulmonary arterial hypertension associated with interferon-beta treatment for multiple sclerosis. Case report and literature review

Demerouti, Eftychia; Karyofyllis, Panagiotis; Athanassopoulos, George; Karatasakis, George; Tsiapras, Dimitrios; Manginas, Athanassios; Voudris, Vasilios

doi:10.1016/j.msard.2019.01.018

Cited by 7 publications

(6 citation statements)

References 16 publications

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“…related genes were increased (Tan et al, 2006;York et al, 2007;Duan et al, 2008;Higgs et al, 2012;Guo et al, 2015;Bodewes et al, 2018). Furthermore, several case reports have emphasized a possible application of type-I interferon therapy to PAH (Anderson et al, 2014;Fok et al, 2016;Demerouti et al, 2019). Our study has also confirmed the notion that type-I FIGURE 6 | Venn diagram and ROC.…”

Section: Discussionsupporting

confidence: 82%

“…Moreover, several studies measuring the type-I interferon signature in PBMCs from SSc patients have consistently revealed that the majority of SSc patients have evidence that type-I interferon related genes were increased ( Tan et al, 2006 ; York et al, 2007 ; Duan et al, 2008 ; Higgs et al, 2012 ; Guo et al, 2015 ; Bodewes et al, 2018 ). Furthermore, several case reports have emphasized a possible application of type-I interferon therapy to PAH ( Anderson et al, 2014 ; Fok et al, 2016 ; Demerouti et al, 2019 ). Our study has also confirmed the notion that type-I interferon may potentially induce PAH in at least some SSc patients reported by Christmann et al (2011) .…”

Section: Discussionmentioning

confidence: 99%

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Identification and Validation of Key Genes Associated With Systemic Sclerosis-Related Pulmonary Hypertension

Zheng

Yan

et al. 2020

Front. Genet.

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Systemic sclerosis-associated with pulmonary arterial hypertension (SSc-PAH) is still a major cause of SSc related deaths. Early diagnosis and prompt treatment are crucial to reduce the mortality of patients with SSc-PAH. To screen the candidate biomarkers and potential therapeutic targets for SSc-PAH, we analyzed the data set (GSE33463 and GSE19617) for confirming key genes in peripheral blood mononuclear cells from SSc-PAH patients. A total of 105 SSc patients from gene expression omnibus (GEO) were included as discovery cohort (n = 69) and duplication cohort (n = 36) for screening hub genes by weighted gene co-expression network analysis (WGCNA). Furthermore, an independent validation cohort (n = 40), including healthy controls, SSc and SSc-PAH patients, was used for further validation by quantitative real-time polymerase chain reaction. The results showed that four key genes, including IFIT2, IFIT3, RSAD2, and PARP14, may serve as potential biomarkers in SSc-PAH. Also, they could be independent risk factors for SSc-PAH. In conclusion, the four key genes can be expected to become the potential therapeutic targets and early biomarkers for accurate therapy and diagnosis of SSc-PAH in the future, which also provides promising insights into the pathogenesis of SSc-PAH at the molecular level.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Key Genes Associated With Systemic Sclerosis-Related Pulmonary Hypertension

Zheng

Yan

et al. 2020

Front. Genet.

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“…3 It still ranges among the first-line therapies in relapse remitting multiple sclerosis (RRMS) to slow down disease progression. 4 While PAH is a rare side effect of IFN-β in RRMS patients, 5 the PAH incidence in this cohort was much higher than expected compared to the general population. 6 In some of these patients, a withdrawal of IFN-β with or without provision of PAH-targeted therapy led to a normalization of hemodynamics.…”

mentioning

confidence: 63%

“…16 The mechanisms by which drugs lead to PAH be often insufficiently understood. This also applies to IFN-β, for which 26 cases of associated PAH have been published to date, 3,5,17 including 11 PAH patients in a cohort of 7190 MS patients treated with IFN-β in the USA between 2001 and 2012. 6 Despite the absence of data demonstrating increased PAH cases due to IFN-β development in randomized controlled trials in MS patients, the published cases, the histopathological findings of typical proliferative lesions in an explanted lung MS lung after treatment with IFN-β 18 and data from interferon receptor knockout (IFNAR −/− ) mice, 19 underline the assumed causal link of IFN-β and PAH.…”

Section: Discussionmentioning

confidence: 99%

Mutually reinforcing effects of genetic variants and interferon‐β 1a therapy for pulmonary arterial hypertension development in multiple sclerosis patients

et al. 2019

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Based on a small number of cases, interferon beta (IFN-β) has been added to the list of drugs that might induce pulmonary arterial hypertension (PAH) in the current European guidelines for the diagnosis and treatment of pulmonary hypertension. Here, we propose that multiple sclerosis patients who are genetically predisposed to PAH may be at higher risk to develop disease when treated with IFN-β. We included two patients with multiple sclerosis who developed a manifest PAH after five amd eight years on IFN-β 1a therapy, respectively (without confirmed right heart catheterization). In both patients, PAH markedly improved after discontinuation of IFN-β 1a and initiation of targeted PAH therapy. For genetic analysis, we used a PAH-gene panel based on next-generation sequencing of 16 PAH and 38 candidate genes. In one of the two patients, we could identify a nonsense variant in the PAH gene ATP13A3. The second patient showed a missense variant of the CYP1B1 gene, which might be linked to PAH predisposition. The results of this study support the hypothesis that multiple sclerosis patients who receive IFN-β 1a therapy might be at higher risk for the development of manifest PAH, if they carry a pathogenic variant or sequence variant genetically predisposing to the disease. However, further studies are necessary to systematically investigate the presence of predisposing PAH gene variants in these patients.

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“…Interferons have been recently identified as an important possible risk factor for PH, after several reports of association of IFN-α [14][15][16][17][18][19], IFN-β [14,16,[20][21][22][23], and experimental models [24][25][26][27] with PH. Some of these cases had reversible PH [28][29][30] and some cases had irreversible PH after exposure to interferons [31][32][33].…”

Section: Etiology and Role Of Interferonmentioning

confidence: 99%

Association of COVID-19 and other viral infections with interstitial lung diseases, pulmonary fibrosis, and pulmonary hypertension: A narrative review

2020

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Background: Interstitial lung diseases (ILDs) include a broad range of diffuse parenchymal lung disorders and are characterized by diffuse parenchymal lung abnormalities leading to irreversible fibrosis. ILDs are correlated with the occurrence of pulmonary fibrosis (PF), which generally also results in pulmonary hypertension (PH). Interferons, secreted in larger amounts during viral infections, are an important possible risk factor contributing to this outcome. Aims: In this narrative review, the role of 10 different viral infections on the generation/development of ILDs and their outcomes are described in detail. The aim of this review is to determine the probable risk that COVID-19 and other viral infections pose in the post-infection development of ILDs, PF, and PH. Methods: Searches in PubMed (Medline), Google Scholar, Web of Science (ISI, Researcher ID, Publons), ResearchGate, Scopus, and secondary sources yielded 134 studies. After exclusion criteria, 92 studies containing the terms "Coronavirus" (COVID-19), "Interstitial Lung Diseases," "Pulmonary Fibrosis," "Pulmonary Hypertension" and "viral infections" were selected for inclusion. Selected articles were read with a focus on the roles of the 10 commonly studied viral infections on generation/intensification of ILDs and classified according to their dominant effect on the respiratory system, with a focus on each infection's effects on parenchyma of the lungs and generation and/or intensification of ILDs. Results: This review found that ILDs, PF, and PH can occur after a COVID-19 viral infection. Similar results are also seen in post-infection cases of other viral infections, including Epstein-Barr virus, Cytomegalovirus, Human herpesvirus-8, adenovirus, Hepatitis C, Torque-Teno (Transfusion-Transmitted) Virus, Human Immunodeficiency Virus, Severe Acute Respiratory Syndrome, and Middle East Respiratory Syndrome. Conclusion: Results of current studies show probable possibility for generation and/or intensification of ILDs in COVID-19 infected patients like other studied viruses. Studies on determination of the actual prevalence of ILD, PF and PH in post-COVID-19 infected patients, follow-up studies on the prevention of ILDs in recovered COVID-19 patients, and meta-analyzed studies on pulmonary outcomes of pandemic corona viruses are strongly recommended as topics for future studies.

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Pulmonary arterial hypertension associated with interferon-beta treatment for multiple sclerosis. Case report and literature review

Cited by 7 publications

References 16 publications

Identification and Validation of Key Genes Associated With Systemic Sclerosis-Related Pulmonary Hypertension

Identification and Validation of Key Genes Associated With Systemic Sclerosis-Related Pulmonary Hypertension

Mutually reinforcing effects of genetic variants and interferon‐β 1a therapy for pulmonary arterial hypertension development in multiple sclerosis patients

Association of COVID-19 and other viral infections with interstitial lung diseases, pulmonary fibrosis, and pulmonary hypertension: A narrative review

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