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.

中文翻译：

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系统性肥大细胞增多症患者血液中 B 细胞、浆细胞和抗体免疫谱的改变。


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 突变的组成性激活肥大细胞 （MC） 扩增，释放 MC 介质，可能作用于肿瘤微环境，包括其他免疫细胞。目的 探讨 SM 患者 B 细胞、浆细胞 （PC） 和抗体同种型区室的血液分布。方法 我们使用光谱流式细胞术和 EuroFlow 免疫监测组和淋巴细胞筛查管量化 108 例 SM 患者血液中的 B 细胞、PC 及其亚群 （35 例骨髓肥大细胞增多症 [BMM] 病例，64 例惰性 SM [ISM] 病例， 9 例侵袭性 SM [ASM] 病例）与 117 名年龄匹配的健康供体和 31 名 SM 患者与 17 名对照患者的配对骨髓样本。同时，测量 IgM 、 IgD 、 IgG 、 IgA 和 IgE 血浆水平。结果与健康供体相比，SM 患者骨髓中未成熟 B 细胞产生增加 （P = .003） 与生发前中心未成熟 （P < .001） 和幼稚 CD5+ B 淋巴细胞 （P < .001） 释放更多有关，但所有不同 IgH 亚型和亚类的 PC 计数显着降低 （P ≤ .001） 以及总体 IgM （P = .001） 和 IgD （P < .001） 血浆水平增加。根据疾病的诊断亚型发现不同的免疫特征，未成熟 B 淋巴细胞血液中的计数逐渐增加，同时 IgMD+、IgG2+、IgA1+ 和 IgA2+ 记忆 B 细胞降低 （P ≤.032） 和 IgM （P = .017） 血浆水平升高在 ASM 病例中，IgM （P = .001） 和 IgD （P = .001） 血浆水平升高在 ISM 病例中， 在 BMM 病例中，IgE 加重 （P < .001） 伴 IgG 水平降低 （P = .008）。 结论 我们的结果显示 SM 患者血液中 B 细胞和 PC 区室的显着失调，与 BMM 患者血浆中抗体同种型谱明显改变一致，与 ISM 与 ASM 一致。