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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. |
- Pechacek, Peter, et al.
(författare)
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Classical polyandry found in the three-toed woodpecker Picoides tridactylus
- 2006
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Ingår i: Journal of Ornithology. - : Springer Science and Business Media LLC. - 0021-8375 .- 2193-7192 .- 2193-7206. ; 147:1, s. 112-114
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Tidskriftsartikel (refereegranskat)abstract
- We report two cases of simultaneous, social polyandry in the three-toed woodpecker Picoides tridactylus found in Berchtesgaden National Park, Germany during an 11-year study. The first case was between two neighbouring pairs in 2003. A female incubated both of her clutches during a period of at least 8 days. The second case was in 2004 between a widowed male and a female of a neighbouring pair. This time, a female divided parental care between her two clutches during a period of at least 27 days. We hypothesise that social polyandry in the three-toed woodpecker may be linked to the parental quality of the first male.
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| 5. |
- Pechacek, Peter, et al.
(författare)
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Monogamy with exceptions: Social and genetic mating system in a bird species with high paternal investment
- 2005
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Ingår i: Behaviour. - : Brill. - 0005-7959 .- 1568-539X. ; 142:8, s. 1093-1114
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Tidskriftsartikel (refereegranskat)abstract
- Animal mating systems are strongly linked to costs and benefits associated with parental care. A high degree of male parental care may explain the occasional occurrence of social polyandry in some monogamous birds such as woodpeckers. We examined mating and parental behaviours of 55 three-toed woodpeckers Picoides tridaclylus, and used DNA fingerprinting to study its genetic mating system over 11 years. Sexes shared nest hole guarding and parental care, but males allocated significantly more time to territory defence, cavity excavation and feeding young than females. Two (7.4%) of the 27 females were polyandrous, each paired simultaneously with two males. Four (7.3%) out of 55 chicks were extra-pair (15.4% of the broods). Two of these chicks were associated with social polyandry, and one with female parasitism. Hence, three-toed woodpeckers were socially and genetically predominantly monogamous. We propose that both social and genetic polyandry in woodpeckers are constrained by the long duration of cavity excavation, few re-mating opportunities, and by the fact that bi-parental care is important for reproductive success.
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