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

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

doi:10.1016/j.jaci.2024.10.005

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

J Allergy Clin Immunol. 2024 Oct 16:S0091-6749(24)01062-5. doi: 10.1016/j.jaci.2024.10.005. Online ahead of print.

Authors

Alba Pérez-Pons¹, Ana Henriques², Teresa Contreras Sanfeliciano³, María Jara-Acevedo⁴, Paula Navarro-Navarro⁴, Andrés C García-Montero¹, Iván Álvarez-Twose⁵, Quentin Lecrevisse⁶, Rafael Fluxa⁷, Laura Sánchez-Muñoz², Carolina Caldas⁸, Julio Pozo⁹, Óscar González-López⁸, Martín Pérez-Andrés⁶, Andrea Mayado¹, Alberto Orfao¹⁰

Affiliations

¹ Cancer Research Center, Department of Medicine and Cytometry Service, University of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain; Biomedical Research Networking Center Consortium, Madrid, Spain; Spanish Network on Mastocytosis, Toledo and Salamanca, Spain.
² Spanish Network on Mastocytosis, Toledo and Salamanca, Spain; Instituto de Estudios de Mastocitosis de Castilla La Mancha, Virgen del Valle Hospital, Toledo and Madrid, Spain.
³ Department of Biochemistry, University Hospital of Salamanca, Salamanca, Spain.
⁴ Cancer Research Center, Department of Medicine and Cytometry Service, University of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain; Biomedical Research Networking Center Consortium, Madrid, Spain; Spanish Network on Mastocytosis, Toledo and Salamanca, Spain; Sequencing Service, University of Salamanca, Salamanca, Spain.
⁵ Biomedical Research Networking Center Consortium, Madrid, Spain; Spanish Network on Mastocytosis, Toledo and Salamanca, Spain; Instituto de Estudios de Mastocitosis de Castilla La Mancha, Virgen del Valle Hospital, Toledo and Madrid, Spain.
⁶ Cancer Research Center, Department of Medicine and Cytometry Service, University of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain; Biomedical Research Networking Center Consortium, Madrid, Spain.
⁷ Cytognos SL, Salamanca, Spain.
⁸ Cancer Research Center, Department of Medicine and Cytometry Service, University of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain; Spanish Network on Mastocytosis, Toledo and Salamanca, Spain.
⁹ Cancer Research Center, Department of Medicine and Cytometry Service, University of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain.
¹⁰ Cancer Research Center, Department of Medicine and Cytometry Service, University of Salamanca, Salamanca, Spain; Biomedical Research Institute of Salamanca, Salamanca, Spain; Biomedical Research Networking Center Consortium, Madrid, Spain; Spanish Network on Mastocytosis, Toledo and Salamanca, Spain. Electronic address: [email protected].

PMID: 39423877
DOI: 10.1016/j.jaci.2024.10.005

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.

Keywords: B lymphocyte; immunoglobulin; mast cell; plasma cell; systemic mastocytosis.