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中性粒细胞与淋巴细胞比值作为系统性硬化症自体造血干细胞移植后临床反应的生物标志物。

Neutrophil-to-lymphocyte ratio as a biomarker for clinical response after autologous haematopoietic stem cell transplantation in systemic sclerosis.

作者信息

Keret Shiri, Kaly Lisa, Schett George, Bergmann Christina, Feldman Erik, Zuckerman Tsila, Yehudai-Ofir Dana, Shouval Aniela, Awisat Abid, Rosner Itzhak, Rozenbaum Michael, Boulman Nina, Sawaed Alaa, Hardak Emilia, Henes Jörg, Slobodin Gleb, Rimar Doron

机构信息

Rheumatology Unit, Faculty of Medicine, Bnai Zion Medical Center, Technion Israel Institute of Technology, Haifa, Israel.

Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.

出版信息

Rheumatology (Oxford). 2025 May 1;64(5):3160-3165. doi: 10.1093/rheumatology/keae606.

Abstract

OBJECTIVE

SSc is a complex disease that affects various target organs, making it difficult to assess response and determine remission or relapse. A baseline neutrophil-to-lymphocyte ratio (NLR) >2.95 is associated with severe progressive skin and lung disease and decreased 5-year survival in SSc. However, it is unknown whether NLR changes in response to treatment. To retrospectively evaluate NLR changes as a biomarker for treatment response in SSc.

METHODS

Progressive diffuse SSc patients who were treated with autologous haematopoietic stem cell transplantation (AHSCT group), with combination therapy of rituximab and MMF (combination group) or chimeric antigen receptor-T-cell (CAR-T) therapy group, were recruited along with healthy controls (HC group). NLR, modified Rodnan Skin Score (mRSS) and forced vital capacity (FVC)% predicted were repeatedly assessed over 2 years.

RESULTS

Fifteen patients were recruited in the AHSCT group, 15 in the combination group and 6 patients in the CAR-T group. Baseline mean NLR was high (>2.95) in AHSCT, combination groups and CAR-T compared with HC. All treatment arms showed a statistically significant decrease in mRSS values and an increase in FVC% at each time point up to 12 months. In a linear mixed model, NLR significantly decreased up to 24 months only in the AHSCT group. NLR correlated with mRSS and FVC exclusively in the AHSCT group. NLR increased above 3 in two patients who experienced a relapse after AHSCT.

CONCLUSION

NLR is a simple biomarker that correlated with outcome measures in SSc following AHSCT but not with conventional therapy or CAR-T therapy. It is suggested that a decrease in NLR following AHSCT may indicate remission, whereas an increase may be associated with exacerbation. Further research is needed to validate these novel findings.

摘要

目的

系统性硬化症(SSc)是一种影响多个靶器官的复杂疾病,难以评估其反应并确定缓解或复发情况。基线中性粒细胞与淋巴细胞比值(NLR)>2.95与SSc患者严重的进行性皮肤和肺部疾病以及5年生存率降低相关。然而,NLR是否会随治疗发生变化尚不清楚。本研究旨在回顾性评估NLR变化作为SSc治疗反应生物标志物的情况。

方法

招募接受自体造血干细胞移植的进行性弥漫性SSc患者(AHSCT组)、接受利妥昔单抗和霉酚酸酯联合治疗的患者(联合治疗组)或嵌合抗原受体T细胞(CAR-T)治疗组的患者,以及健康对照者(HC组)。在2年时间内反复评估NLR、改良Rodnan皮肤评分(mRSS)和预测的用力肺活量(FVC)%。

结果

AHSCT组招募了15例患者,联合治疗组15例,CAR-T组6例。与HC组相比,AHSCT组与联合治疗组以及CAR-T组的基线平均NLR较高(>2.95)。在所有治疗组中,直至12个月的每个时间点,mRSS值均有统计学意义的下降,FVC%均有上升。在线性混合模型中,仅AHSCT组的NLR在24个月内显著下降。仅在AHSCT组中,NLR与mRSS和FVC相关。在AHSCT后复发的2例患者中,NLR升高至3以上。

结论

NLR是一种简单的生物标志物,与AHSCT后SSc的预后指标相关,但与传统治疗或CAR-T治疗无关。提示AHSCT后NLR下降可能表明缓解,而升高可能与病情加重有关。需要进一步研究来验证这些新发现。

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