The Journal of allergy and clinical immunology · 2024
Human DNA-dependent protein kinase catalytic subunit deficiency: A comprehensive review and update.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Adelon Jihane, Abolhassani Hassan, Esenboga Saliha, Fouyssac Fanny, Cagdas Deniz, Tezcan Ilhan, Kuskonmaz Barıs, Cetinkaya Duygu, Suarez Felipe, Mahdaviani Seyed Alireza, Plassart Samira, Mathieu Anne-Laure, Fabien Nicole, Malcus Christophe, Morfin-Sherpa Florence, Billaud Geneviève, Tusseau Maud, Benezech Sarah, Walzer Thierry, De Villartay Jean-Pierre, Bertrand Yves, Belot Alexandre
Аннотация
BACKGROUND: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has an essential role in the non-homologous end-joining pathway that repairs DNA double-strand breaks in V(D)J recombination involved in the expression of T- and B-cell receptors. Whereas homozygous mutations in Prkdc define the Scid mouse, a model that has been widely used in biology, human mutations in PRKDC are extremely rare and the disease spectrum has not been described so far.
OBJECTIVES: To provide an update on the genetics, clinical spectrum, immunological profile, and therapy of DNA-PKcs deficiency in human.
METHODS: The clinical, biological, and treatment data from the 6 cases published to date and from 1 new patient were obtained and analyzed. Rubella PCR was performed on available granuloma material.
RESULTS: We report on 7 patients; 6 patients displayed the autosomal recessive p.L3062R mutation in PRKDC-encoding DNA-PKcs. Atypical severe combined immunodeficiency with inflammatory lesions, granulomas, and autoimmunity was the predominant clinical manifestation (n = 5 of 7). Rubella viral strain was detected in the granuloma of 1 patient over the 2 tested. T-cell counts, including naive CD4+CD45RA+ T cells and T-cell function were low at diagnosis for 6 patients. For most patients with available values, naive CD4+CD45RA+ T cells decreased over time (n = 5 of 6). Hematopoietic stem cell transplantation was performed in 5 patients, of whom 4 are still alive without transplant-related morbidity. Sustained T- and B-cell reconstitution was observed, respectively, for 4 and 3 patients, after a median follow-up of 8 years (range 3-16 years).
CONCLUSIONS: DNA-PKcs deficiency mainly manifests as an inflammatory disease with granuloma and autoimmune features, along with severe infections.
OBJECTIVES: To provide an update on the genetics, clinical spectrum, immunological profile, and therapy of DNA-PKcs deficiency in human.
METHODS: The clinical, biological, and treatment data from the 6 cases published to date and from 1 new patient were obtained and analyzed. Rubella PCR was performed on available granuloma material.
RESULTS: We report on 7 patients; 6 patients displayed the autosomal recessive p.L3062R mutation in PRKDC-encoding DNA-PKcs. Atypical severe combined immunodeficiency with inflammatory lesions, granulomas, and autoimmunity was the predominant clinical manifestation (n = 5 of 7). Rubella viral strain was detected in the granuloma of 1 patient over the 2 tested. T-cell counts, including naive CD4+CD45RA+ T cells and T-cell function were low at diagnosis for 6 patients. For most patients with available values, naive CD4+CD45RA+ T cells decreased over time (n = 5 of 6). Hematopoietic stem cell transplantation was performed in 5 patients, of whom 4 are still alive without transplant-related morbidity. Sustained T- and B-cell reconstitution was observed, respectively, for 4 and 3 patients, after a median follow-up of 8 years (range 3-16 years).
CONCLUSIONS: DNA-PKcs deficiency mainly manifests as an inflammatory disease with granuloma and autoimmune features, along with severe infections.