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- Oikonomou, Vasileios, et al.
(författare)
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The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1.
- 2024
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Ingår i: The New England journal of medicine. - 1533-4406. ; 390:20, s. 1873-1884
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood.We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses.Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients.Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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| 2. |
- Sulaiman, Naji, et al.
(författare)
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Cultural vs. state borders : plant foraging by Hawraman and Mukriyan kurds in western Iran
- 2024
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Ingår i: PLANTS. - : MDPI. - 2223-7747. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Plant foraging is a millennia-old activity still practiced by many people in the Middle East, particularly in the Fertile Crescent region, where several socioeconomic, ecological, and cultural factors shape this practice. This study seeks to understand the drivers of plant foraging in this complex region characterized by highly diverse linguistic, religious, and cultural groups. Our study aims to document the wild plants used by Kurds in Western Iran, identify similarities and differences among Hawraman and Mukriyan Kurdish groups in Iran, and compare our findings with a previous study on the Hawramani in Iraq. Forty-three semi-structured in-depth interviews were conducted in Kurdish villages of Western Iran. The results revealed the use of 44 wild food plant taxa, their preparation, and culinary uses. Among the reported taxa, 28 plant taxa were used by Mukriyani, and 33 by Hawramani. The study revealed a significant difference between the Hawraman and Mukriyan regions in Iran, whereas there is a high similarity between Hawramani Kurds in Iran and Iraq. We found that the invisible cultural border carries more weight than political divisions, and this calls for a paradigm shift in how we perceive and map the distribution of ethnobotanical knowledge.
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