ILT-2 and ILT-4 expression and donor genotype as factors associated with HSCT outcome.

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2025-10-02 DOI:10.1016/j.clim.2025.110605

Jagoda Siemaszko, Piotr Łacina, Donata Szymczak, Agnieszka Szeremet, Maciej Majcherek, Anna Czyż, Małgorzata Sobczyk-Kruszelnicka, Wojciech Fidyk, Iwona Solarska, Barbara Nasiłowska-Adamska, Patrycja Skowrońska, Maria Bieniaszewska, Agnieszka Tomaszewska, Grzegorz W Basak, Sebastian Giebel, Tomasz Wróbel, Katarzyna Bogunia-Kubik

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引用次数: 0

Abstract

Background: NK cell activity after allogeneic haematopoietic stem cell transplantation (HSCT) is still not fully understood. Their cytotoxic activity is modulated by a range of inhibitory and activating surface receptors. Among these, the inhibitory receptors ILT-2 and ILT-4 have yet to be explored in relation to HSCT and its outcomes.

Methods: Genotyping for ILT-2 and ILT-4 was performed using TaqMan assays. ILT-2 and ILT-4 surface expression on NK cells was assessed by flow cytometry. Levels of sHLA-F and sHLA-G were determined using ELISA. mRNA expression of ILT-2, ILT-4 and IFN-γ was measured with quantitative real-time PCR with TaqMan Gene Expression probes.

Results: Presence of donor ILT-2 rs1061681 T allele was associated with increased risk of chronic graft-versus-host disease (cGVHD) (p = 0.0239). Donor ILT-4 rs1128646 T allele was related with decreased risk of overall survival after HSCT (p = 0.0506) and with higher risk of acute GvHD (aGvHD) (p = 0.0834). Serum levels of sHLA-F and sHLA-G were significantly higher at day +30 than day +90 after HSCT (p = 0.0002 and p < 0.0001, respectively). Expression of ILT2 at mRNA level was significantly decreased among recipients with aGvHD (p = 0.0266). ILT-4 expression correlated negatively with expression of interferon gamma (p = 0.0280, R = -0.532). The percentages of LILRB1/ILT-2+ and LILRB2/ILT4+ NK cells were the highest at day +21 after HSCT (p = 0.0014 and p < 0.0001 for ILT-2 and ILT-4, respectively).

Conclusions: Both ILT-2 and ILT-4 inhibitory receptors were found to be associated with allogeneic HSCT outcome. This suggests that ILT receptor expression on NK cells may potentially play a role in post-transplant complications.

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il -2和il -4表达和供体基因型与HSCT结果相关。

背景：同种异体造血干细胞移植（HSCT）后NK细胞的活性尚不完全清楚。它们的细胞毒性活性受一系列抑制和激活表面受体的调节。其中，抑制受体ILT-2和ILT-4与HSCT及其结果的关系尚待探讨。方法：采用TaqMan法对ILT-2和ILT-4进行基因分型。流式细胞术检测NK细胞表面ILT-2和ILT-4的表达。ELISA法检测sHLA-F、sHLA-G水平。采用TaqMan基因表达探针，实时荧光定量PCR检测ILT-2、ILT-4和IFN-γ mRNA表达。结果：供体il -2 rs1061681 T等位基因的存在与慢性移植物抗宿主病（cGVHD）的风险增加相关（p = 0.0239）。供体il -4 rs1128646 T等位基因与HSCT术后总生存风险降低相关（p = 0.0506），与急性GvHD （aGvHD）风险升高相关（p = 0.0834）。血清sHLA-F和sHLA-G水平在HSCT后+30天显著高于+90天（p = 0.0002和p ）结论：发现ILT-2和ILT-4抑制受体与同种异体HSCT预后相关。这表明NK细胞上ILT受体的表达可能在移植后并发症中起潜在的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.