Altered B-cell, plasma cell and antibody immune profiles in blood of systemic mastocytosis.

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology Pub Date : 2024-10-16 DOI:10.1016/j.jaci.2024.10.005

Alba Pérez-Pons,Ana Henriques,Teresa Contreras Sanfeliciano,María Jara-Acevedo,Paula Navarro-Navarro,Andrés C García-Montero,Iván Álvarez-Twose,Quentin Lecrevisse,Rafael Fluxa,Laura Sánchez-Muñoz,Carolina Caldas,Julio Pozo,Óscar González-López,Martín Pérez-Andrés,Andrea Mayado,Alberto Orfao

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引用次数: 0

Abstract

BACKGROUND Systemic mastocytosis (SM) is a heterogeneous disease characterised by an expansion of KIT-mutated constitutively activated mast cells (MC) which release MC mediators that might act on the tumour microenvironment including other immune cells. OBJECTIVE Here we investigated the blood distribution of B-cell, plasma cell (PC) and antibody-isotype compartments in SM. METHODS We used spectral flow cytometry and the EuroFlow Immunomonitoring panel and Lymphocyte Screening Tube to quantify B-cells, PC and their subsets in blood of 108 SM patients - 35 bone marrow mastocytosis (BMM), 64 indolent SM (ISM), 9 aggressive SM (ASM)- vs 117 age-matched healthy donors (HD) and paired bone marrow (BM) samples of 31 SM vs 17 controls, respectively. In parallel, immunoglobulin (Ig) M, IgD, IgG, IgA and IgE plasma levels of were measured. RESULTS Compared to HD, SM patients showed an increased immature B-cell production in BM (P=0.003) associated with a greater release of pre-germinal center immature (P<0.001) and naive CD5+ B-lymphocytes (P<0.001) to blood, but a pronounced decrease in PC counts of all different IgH-isotypes and subclasses (P≤0.001) together with overall increased IgM (P=0.001) and IgD (P<0.001) plasma levels. Of note, different immune profiles were found per diagnostic subtype of the disease with progressively greater counts in blood of immature B-lymphocytes together with decreased IgMD+, IgG2+, IgA1+ and IgA2+ MBC (P≤0.032) and elevated IgM (P=0.017) plasma levels in ASM cases, increased IgM (P=0.001) and IgD (P=0.001) plasma levels in ISM patients and exacerbated IgE (P<0.001) with decreased IgG (P=0.008) plasma levels in BMM cases. CONCLUSION Our results reveal a significant dysregulation of the B-cell and PC compartments in blood of SM patients, consistent with distinctly altered antibody-isotype profiles in plasma of BMM vs ISM vs ASM patients.

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全身性肥大细胞增多症患者血液中的 B 细胞、浆细胞和抗体免疫谱发生变化。

背景系统性肥大细胞增多症（SM）是一种异质性疾病，其特征是 KIT 突变的组成型活化肥大细胞（MC）的扩增，MC 释放的介质可能对肿瘤微环境（包括其他免疫细胞）产生作用。方法我们使用光谱流式细胞仪和 EuroFlow 免疫监测板及淋巴细胞筛查管，分别量化了 108 例 SM 患者（35 例骨髓肥大细胞增多症（BMM）、64 例惰性 SM（ISM）、9 例侵袭性 SM（ASM））与 117 例年龄匹配的健康供体（HD）血液中的 B 细胞、浆细胞及其亚群，以及 31 例 SM 与 17 例对照的配对骨髓（BM）样本。结果与 HD 相比，SM 患者的骨髓中未成熟 B 细胞生成增加（P=0.003），与前生殖中心未成熟（P<0.001）和天真 CD5+ B 淋巴细胞（P<0.001）释放到血液中，但所有不同 IgH-isotypes 和亚类的 PC 数量明显减少（P≤0.001），同时 IgM（P=0.001）和 IgD（P<0.001）血浆水平总体升高。值得注意的是，每种疾病诊断亚型都有不同的免疫特征，在 ASM 病例中，血液中未成熟 B 淋巴细胞的数量逐渐增加，IgMD+、IgG2+、IgA1+ 和 IgA2+ MBC 减少（P≤0.032），IgM（P=0.017）血浆水平升高；在 ASM 病例中，IgM（P=0.001）和 IgD（P=0.结论我们的研究结果表明，SM 患者血液中的 B 细胞和 PC 区明显失调，这与 BMM vs ISM vs ASM 患者血浆中明显改变的抗体异型图谱一致。

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来源期刊

Journal of Allergy and Clinical Immunology 医学-过敏

CiteScore

25.90

自引率

7.70%

发文量

1302

审稿时长

38 days

期刊介绍： The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.