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

IF 11.2 1区医学 Q1 ALLERGY Journal of Allergy and Clinical Immunology Pub Date : 2025-02-01 Epub Date: 2024-10-16 DOI:10.1016/j.jaci.2024.10.005

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

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Abstract

Background

Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated constitutively activated mast cells (MCs) that release MC mediators, which might act on the tumor microenvironment including other immune cells.

Objective

To investigate the blood distribution of B-cell, plasma cell (PC), and antibody isotype compartments in patients with SM.

Methods

We used spectral flow cytometry and the EuroFlow Immunomonitoring panel and Lymphocyte Screening Tube to quantify B cells, PCs, and their subsets in blood of 108 patients with SM (35 bone marrow mastocytosis [BMM] cases, 64 indolent SM [ISM] cases, 9 aggressive SM [ASM] cases) versus 117 age-matched healthy donors and paired bone marrow samples of 31 patients with SM versus 17 controls, respectively. In parallel, IgM, IgD, IgG, IgA, and IgE plasma levels were measured.

Results

Compared with healthy donors, patients with SM showed increased immature B-cell production in bone marrow (P = .003) associated with greater release of pre–germinal center immature (P < .001) and naive CD5⁺ B lymphocytes (P < .001) to blood, but a pronounced decrease in PC counts of all different IgH isotypes and subclasses (P ≤ .001) together with overall increased IgM (P = .001) and IgD (P < .001) plasma levels. Different immune profiles were found per diagnostic subtype of disease with progressively greater counts in blood of immature B lymphocytes together with decreased IgMD⁺, IgG2⁺, IgA1⁺, and IgA2⁺ memory B cells (P ≤ .032) and elevated IgM (P = .017) plasma levels in cases of ASM, increased IgM (P = .001) and IgD (P = .001) plasma levels in ISM cases, and exacerbated IgE (P < .001) with decreased IgG (P = .008) plasma levels in BMM cases.

Conclusions

Our results reveal a significant dysregulation of the B-cell and PC compartments in blood of patients with SM, consistent with distinctly altered antibody isotype profiles in plasma of patients with BMM versus ISM versus ASM.

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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。

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

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.