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.