Bernatowska Ewa, Pac Małgorzata, Heropolitańska-Pliszka Edyta, Pietrucha Barbara, Dąbrowska-Leonik Nel, Skomska-Pawliszak Małgorzata, Bernat-Sitarz Katarzyna, Krzysztopa-Grzybowska Katarzyna, Wolska-Kuśnierz Beata, Bohynikova Nadia, Augustynowicz Ewa, Augustynowicz-Kopeć Ewa, Korzeniewska-Koseła Maria, Wieteska-Klimczak Anna, Książyk Janusz, Jackowska Teresa, van den Burg Mirjam, Casanova Jean-Laurent, Picard Capucine, Mikołuć Bożena
Department of Immunology, Children's Memorial Health Institute, Warsaw, Poland.
Department of Sera and Vaccines Evaluation, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.
Front Pediatr. 2022 May 19;10:839111. doi: 10.3389/fped.2022.839111. eCollection 2022.
We aimed to assess BCG (Bacillus Calmette-Guérin) complications in patients with Inborn Errors of Immunity (IEI), according to the inherited disorders and associated immunological defects, as well as the different BCG substrains.
We studied adverse reactions to the locally-produced BCG Moreau vaccine, analyzed in patients with IEI diagnosed between 1980 and 2020 in the Department of Immunology, Children's Memorial Health Institute (CMHI), Warsaw. These results were compared with previously published studies.
Significantly fewer disseminated BCG infections (BCGosis) were found in 11 of 72 (15%) SCID (Severe Combined Immunodeficiency) NK (Natural Killer)-phenotype patients, when compared with the 119 out of 349 (34%) ( = 0.0012) patients with SCID with BCG in other countries. Significantly fewer deaths caused by BCGosis were observed ( = 0.0402). A significantly higher number of hematopoietic stem cell transplantations (HSCTs) were performed in the CMHI study ( = 0.00001). BCGosis was found in six patients with Mendelian susceptibility to mycobacterial diseases (MSMD). Other patients with IEI prone to BCG complications, such as CGD (Chronic Granulomatous Disease), showed no case of BCGosis.
The BCG Moreau substrain vaccine, produced in Poland since 1955, showed genetic differences with its parental Brazilian substrain together with a superior clinical safety profile in comparison with the other BCG substrains, with no BCGosis in patients with IEI other than SCID and MSMD. Our data also confirmed significantly fewer cases of BCGosis and deaths caused by BCG infection in patients with SCID with this vaccine substrain. Finally, they confirmed the protecting role of NK cells, probably their production of IFN-γ.
我们旨在根据遗传性疾病和相关免疫缺陷以及不同的卡介苗亚菌株，评估免疫缺陷病（IEI）患者中的卡介苗（BCG，即卡介苗）并发症情况。
我们研究了对本地生产的卡介苗莫罗疫苗的不良反应，这些反应在华沙儿童纪念健康研究所（CMHI）免疫科1980年至2020年期间诊断的IEI患者中进行分析。将这些结果与先前发表的研究进行比较。
在72例（15%）严重联合免疫缺陷（SCID）自然杀伤（NK）表型患者中，发现播散性卡介苗感染（卡介苗病）的病例明显少于其他国家349例（34%）（P = 0.0012）患有卡介苗的SCID患者中的119例。观察到由卡介苗病导致的死亡明显更少（P = 0.0402）。在CMHI研究中进行造血干细胞移植（HSCT）的数量明显更多（P = 0.00001）。在6例孟德尔遗传性分枝杆菌易感性疾病（MSMD）患者中发现了卡介苗病。其他易发生卡介苗并发症的IEI患者，如慢性肉芽肿病（CGD），未出现卡介苗病病例。
自195年以来在波兰生产的卡介苗莫罗亚菌株疫苗与其亲本巴西亚菌株存在基因差异，并且与其他卡介苗亚菌株相比临床安全性更高，除SCID和MSMD患者外，IEI患者中未出现卡介苗病。我们的数据还证实，使用这种疫苗亚菌株的SCID患者中，卡介苗病病例和由卡介苗感染导致的死亡明显更少。最后，它们证实了NK细胞的保护作用，可能是其产生干扰素-γ的作用。
