Leukemic B cells expression of CD200 and Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, CD305) in Chronic Lymphocytic Leukemia patients in relation to Treg frequency

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2024-10-21 DOI:10.1016/j.prp.2024.155669

Reham Hammad , Eman Z. Kandeel , Claude Lambert , Ulrich Sack , Sandy Kujumdshiev , Arwa Kamhawy , Omaima I. Abo-Elkheir , Fatma EL-Zahraa Abd El Hakam , Alya Mashaal , Mohammed Ramadan , Abdel-Aziz A. Zidan , Nadia M. Hamdy

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Abstract

Background

Chronic lymphocytic leukemia (CLL) is characterized by a wide range of tumor-induced immune alterations. Regulatory T cells (Treg) play a central role in these immune responses. CD200 and Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, CD305) are inhibitory markers said to be involved in Treg immune response. We aimed to analyze the expression of CD200 and LAIR-1 on leukemic cells and assess their interactions with the Treg frequency to elucidate their role in the CLL course.

Subjects and methods

This study was conducted on 70 participants: 50 newly diagnosed CLL cases classified according to Rai staging system into group 1 (n = 25) patients with stages 0, I, and II, and group 2 (n = 25) of advanced patients with stages III and IV. In addition to control group (n = 20) of healthy adults. Flow cytometry was used to investigate Treg frequency in bone marrow (BM) proportional to CD4+ T cell and to assess leukemic cell expression of CD200 and LAIR-1. Also, in-silico database analysis was performed to identify study markers interactions for future personalized target therapy.

Results

Comparison between CLL groups 1 and 2 revealed increased leukemic cell percentage expressing LAIR-1 (p = 0.021) in group 1. Group 2 showed significant increase in frequency of Treg in BM and leukemic cells expressing CD200. There was a strong positive correlation between frequency of Treg and leukemic cells expressing CD200 (r = 0.669, p = 0.000). On the other hand, there was a negative correlation between frequency of Treg and leukemic cell expressing LAIR-1 (r = −0.342, p = 0.015). ROC curve analysis revealed that increased frequency of leukemic cells expressing CD200 yielded sensitivity (SN) and specificity (SP) of 96 % and 84 %, respectively in detecting CLL progression, with an AUC of 0.965. Leukemic cell percentages expressing LAIR-1 yielded a lower SN (75 %), SP (72 %), with an AUC of 0.688.

Conclusion

Treg frequency in BM was significantly increased in CLL advanced stages according to Rai classification. Leukemic cells CD200 and LAIR-1 expression were differently associated with Treg frequency. Increased CD200 expressions on leukemic cells can be considered a sensitive and specific biomarker in detecting CLL progression. As demonstrated by the in-silico research, CD200 blockade targeting may offer therapeutic benefits for CLL treatment through Treg suppression.

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慢性淋巴细胞白血病患者白血病 B 细胞 CD200 和白细胞相关免疫球蛋白样受体-1 (LAIR-1, CD305) 的表达与 Treg 频率的关系

背景慢性淋巴细胞白血病（CLL）的特点是由肿瘤诱发的多种免疫改变。调节性 T 细胞（Treg）在这些免疫反应中发挥着核心作用。据说，CD200和白细胞相关免疫球蛋白样受体-1（LAIR-1，CD305）是参与Treg免疫反应的抑制性标志物。我们旨在分析 CD200 和 LAIR-1 在白血病细胞上的表达，并评估它们与 Treg 频率的相互作用，以阐明它们在 CLL 病程中的作用：50例新诊断的CLL病例，根据Rai分期系统分为第1组（n = 25）0期、I期和II期患者和第2组（n = 25）III期和IV期晚期患者。此外还有健康成人对照组（n = 20）。流式细胞术用于研究骨髓（BM）中与 CD4+ T 细胞成比例的 Treg 频率，并评估白血病细胞的 CD200 和 LAIR-1 表达。结果CLL第1组和第2组之间的比较显示，第1组表达LAIR-1的白血病细胞百分比增加（p = 0.021），第2组骨髓中Treg的频率和表达CD200的白血病细胞显著增加。Treg 的频率与表达 CD200 的白血病细胞之间存在很强的正相关性（r = 0.669，p = 0.000）。另一方面，Treg的频率与表达LAIR-1的白血病细胞之间呈负相关（r = -0.342，p = 0.015）。ROC 曲线分析显示，白血病细胞表达 CD200 的频率增加对检测 CLL 进展的敏感性（SN）和特异性（SP）分别为 96% 和 84%，AUC 为 0.965。表达 LAIR-1 的白血病细胞百分比的灵敏度（SN）（75%）和特异度（SP）（72%）较低，AUC 为 0.688。白血病细胞 CD200 和 LAIR-1 的表达与 Treg 频率有不同的相关性。白血病细胞 CD200 表达的增加可被视为检测 CLL 进展的敏感而特异的生物标志物。正如体内研究结果所证明的那样，CD200靶向阻断可通过抑制Treg为CLL治疗提供疗效。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.