Siemaszko Jagoda, Łacina Piotr, Szymczak Donata, Szeremet Agnieszka, Majcherek Maciej, Czyż Anna, Sobczyk-Kruszelnicka Małgorzata, Fidyk Wojciech, Solarska Iwona, Nasiłowska-Adamska Barbara, Skowrońska Patrycja, Bieniaszewska Maria, Tomaszewska Agnieszka, Basak Grzegorz W, Giebel Sebastian, Wróbel Tomasz, Bogunia-Kubik Katarzyna
Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Department and Clinic of Hematology, Cellular Therapies and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland.
Hum Immunol. 2024 Nov;85(6):111147. doi: 10.1016/j.humimm.2024.111147. Epub 2024 Sep 26.
Despite new treatment strategies, graft-versus-host disease (GvHD) remains a formidable complication after allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the impact of polymorphisms and expression of MICA and NKG2D receptor on the development of GvHD in allogeneic HSCT recipients. Soluble MICA (sMICA) concentration was measured in serum collected 30 days after transplantation and the genetic variability of MICA and NKG2D genes was evaluated. The frequency of NKG2D+NK cells was determined by flow cytometry before and (21, 30, 60 and 90 days) after transplantation. Recipients with acute GvHD grades II-IV carried the NKG2D rs1049174 C allele more frequently than controls or patients with no or mild disease. Patients with chronic GvHD had higher frequency of NKG2D expressing NK cells posttransplant, reflecting increased activity of their NK cells. Although no direct relationship between MICA SNPs and GvHD were observed, the presence of MICA rs1051792 GG genotype correlated with elevated sMICA levels and increased serum level of sMICA was associated with higher risk of chronic GvHD. Our findings suggest that sMICA concentration may serve as a potential biomarker for chronic GvHD and emphasize the impact of genetic variability of NKG2D and its surface expression on the HSCT outcome.
尽管有了新的治疗策略，但移植物抗宿主病（GvHD）仍然是异基因造血干细胞移植（HSCT）后一个棘手的并发症。本研究旨在探讨MICA和NKG2D受体的多态性及表达对异基因HSCT受者发生GvHD的影响。在移植后30天采集的血清中检测可溶性MICA（sMICA）浓度，并评估MICA和NKG2D基因的遗传变异性。通过流式细胞术测定移植前及移植后（21、30、60和90天）NKG2D+NK细胞的频率。急性GvHD II-IV级的受者比对照组或无病或轻症患者更频繁地携带NKG2D rs1049174 C等位基因。慢性GvHD患者移植后表达NKG2D的NK细胞频率更高，反映出其NK细胞活性增加。虽然未观察到MICA单核苷酸多态性与GvHD之间的直接关系，但MICA rs1051792 GG基因型的存在与sMICA水平升高相关，且sMICA血清水平升高与慢性GvHD风险增加有关。我们的研究结果表明，sMICA浓度可能作为慢性GvHD的潜在生物标志物，并强调了NKG2D的遗传变异性及其表面表达对HSCT结果的影响。
