San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Via Olgettina, 60, 20123, Milan, Italy.
Paediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Clin Immunol. 2022 Nov;42(8):1742-1747. doi: 10.1007/s10875-022-01338-x. Epub 2022 Aug 10.
X-linked chronic granulomatous disease is a rare disease caused by mutations in the CYBB gene. While more extensive knowledge is available on genetics, pathogenesis, and possible therapeutic options, mitochondrial activity and its implications on patient monitoring are still not well-characterized. We have developed a novel protocol to study mitochondrial activity on whole blood of XCGD patients before and after transplantation, as well as on XCGD carriers. Here we present results of these analyses and of the restoration of mitochondrial activity in hyperinflamed X-linked Chronic Granulomatous Disease after hematopoietic stem cell transplantation. Moreover, we show a strong direct correlation between mitochondrial activity, chimerism, and DHR monitored before and after transplantation and in XCGD carriers. In conclusion, based on these findings, we suggest testing this new ready-to-use marker to better characterize patients before and after treatment and to investigate disease expression in carriers.
X 连锁慢性肉芽肿病是一种由 CYBB 基因突变引起的罕见疾病。虽然人们对其遗传学、发病机制和可能的治疗选择有了更广泛的了解，但线粒体活性及其对患者监测的影响仍未得到很好的描述。我们开发了一种新的方案，用于研究 XCGD 患者移植前后及 XCGD 携带者的全血中线粒体活性。在此，我们呈现了这些分析的结果，以及造血干细胞移植后过度炎症性 X 连锁慢性肉芽肿病中线粒体活性的恢复情况。此外，我们还显示了移植前后和 XCGD 携带者中线粒体活性、嵌合体和 DHR 之间的直接强相关性。总之，基于这些发现，我们建议使用这种新的即用型标志物进行检测，以更好地在治疗前后对患者进行特征描述，并研究携带者中的疾病表达。
