Altered B-cell, Plasma Cell, and Antibody Immune Profiles in Blood of Patients with Systemic Mastocytosis.

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.