Newly discovered genetic defect disrupts blood formation and immunesystem nejm
affecting various organs such as the kidneys, intestines, and skin. The treating physician then contacted the St. Anna CCRI providing blood samples from the patient, and was successful. The internationally leading center for rare diseases of blood formation and the immune system found the cause.
"Initially, we had only one patient and therefore did not know which symptoms were related to the gene defect and which were just additional accompanying manifestations. That was quite a challenge," says Jana Block, first author of the publication and a PhD student in Boztug's research group at St. Anna CCRI and CeMM. Credit: St.
"The protein appears to play a role in keeping the activation of T cells within a certain range," explains Block. This is important because overactivation can lead to damage to surrounding tissues and organs, especially in the absence of an actual pathogen. A connection between T-cell defects and predisposition to tumor diseases is observed in other immune deficiencies and cannot be ruled out in the case of DOCK11 deficiency.
United Kingdom Latest News, United Kingdom Headlines
Similar News:You can also read news stories similar to this one that we have collected from other news sources.
Homocysteine promotes atherosclerosis through macrophage pyroptosis via endoplasmic reticulum stress and calcium disorder - Molecular MedicineBackground Elevated plasma homocysteine levels, known as hyperhomocysteinemia, have been identified as an independent risk factor for atherosclerosis and related cardiovascular diseases. Macrophage pyroptosis-mediated inflammation is crucial in the development of atherosclerosis, but the underlying mechanisms remain unclear. Methods A hyperhomocysteinemia atherosclerotic model with ApoE−/− mice fed with a high-methionine diet was constructed to investigate the role of plasma homocysteine in atherosclerosis. THP-1-derived macrophages were used to investigate the mechanisms by which Hcy regulates pyroptosis. Results We found that hyperhomocysteinemia resulted in larger atherosclerotic plaques and more secretion of inflammatory cytokines, while these effects were attenuated in Caspase-1 knockdown mice. Likewise, in vitro experiments demonstrated that treatment of macrophages with homocysteine resulted in NLRP3 inflammasome activation and pyroptosis, as evidenced by cleavage of Caspase-1, production of downstream IL-1β, elevation of lactate dehydrogenase activity, and extensive propidium iodide-positive staining of cells. These were all inhibited by Caspase-1 inhibitor. In addition, excessive generation of reactive oxygen species was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential and ATP synthesis. Moreover, further experiments revealed that homocysteine induced endoplasmic reticulum stress, enhanced communication between the endoplasmic reticulum and mitochondria, and consequently contributed to calcium disorder. Furthermore, the endoplasmic reticulum stress inhibitor, 4PBA, the calcium chelator, BAPTA, and calcium channel inhibitor, 2-APB significantly improved macrophage pyroptosis. Conclusion Homocysteine accelerates atherosclerosis progression by enhancing macrophages pyroptosis via promoting endoplasmic reticulum stress, endoplasmic reticulum-mitochondria coupling, and disturbing of calcium disorder.
Read more »
NHS partner Livi takes medicine with new round of layoffsLivi, which is owned by the Swedish digital health company Kry, is making about 10% of its non-clinical UK workforce redundant, Sky News understands.
Read more »
Dear Anna Richardson: How do I tell my family about my partner after coming out?For Pride Month, Anna Richardson is taking on the role of one of Metro's Agony Aunts 🏳️🌈 She's here to give advice on telling your family about your partner 👇
Read more »
Anna Richardson says celebs are desperate to strip off for Naked AttractionAnna Richardson has opened up on the bunch of eager celebrities who are desperate to strip off for a celebrity special on the hit Channel 4 show Naked Attraction
Read more »
Mums are skipping meals to feed their children says new research75 per cent of those surveyed said that food shopping caused 'serious financial stress'
Read more »