Altered leukocyte subsets and immune proteome indicate proinflammatory mechanisms in mastocytosis

Hermans, Maud A.W.; Heeringa, Jorn J.; Swagemakers, S.G.A.; Schrijver, Benjamin; Daele, Paul L A van; Spek, Peter J. van der; Hagen, P. Martin van; Zelm, Menno C. van; Dik, Willem A.

doi:10.1016/j.jaci.2021.12.786

Cited by 8 publications

(14 citation statements)

References 34 publications

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“…Here we demonstrated that SM patients do exhibit important numerical alterations of blood circulating monocyte and DC populations, in addition to their functional activation. Thus, we confirmed previous data showing decreased total monocyte and DC counts in SM 38 . Decreased monocyte counts were at the expense of both iMo and specific (SLAN + CD36 − and SLAN + CD36 + ) subsets of ncMo.…”

Section: Discussionsupporting

confidence: 92%

“…These findings suggest that DC might also undergo increased migration to tissues where clonal MC accumulate. Altogether, these results support and extend on previous observations38 suggesting that clonal MC might produce proteases that affect the skin environment and activate keratinocytes to produce CCL19, in addition to MCP-1/CCL2, (a chemokine that Surface membrane expression levels of the CD192/CXCR2 chemokine receptor on circulating blood monocytes and their subsets in healthy donors (HD) versus systemic mastocytosis (SM) patients (A and C) distributed according to the diagnostic subtype of the disease (B and D). Notched-boxes extend from 25th to 75th percentile values, the lines in the middle and vertical lines correspond to median values and the 10th and 90th percentiles, respectively, and the dots represent each individual case studied.…”

supporting

confidence: 93%

“…In line with these observations, previous studies in SM have recurrently reported abnormally high cytokine levels in plasma 25,27,38,39 . Interestingly, these have been repeatedly suggested to derive from an increased production by the pathologic MC 25 .…”

Section: Discussionsupporting

confidence: 67%

“…37 In line with these observations, previous studies in SM have recurrently reported abnormally high cytokine levels in plasma. 25,27,38,39 Interestingly, these have been repeatedly suggested to derive from an increased production by the pathologic MC. 25 Despite this, data on cytokine production by purified primary MC could not confirm an increased production of inflammatory cytokines at the mRNA level.…”

Section: Discussionmentioning

confidence: 99%

“…In parallel, they also found decreased percentages of pDC and monocytes together with an increased proportion of Th2 cells in another group of 18 ISM patients, suggesting signs of broad immune activation, beyond, MC in SM. 38 However, functional analysis of the numerically altered immune cells is still missing.…”

Section: Discussionmentioning

confidence: 99%

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Altered innate immune profile in blood of systemic mastocytosis patients

Pérez-Pons

Jara‐Acevedo

Henriques

et al. 2022

Clinical & Translational All

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Background Mast cells (MC) from systemic mastocytosis (SM) patients release MC mediators that lead to an altered microenvironment with potential consequences on innate immune cells, such as monocytes and dendritic cells (DC). Here we investigated the distribution and functional behaviour of different populations of blood monocytes and DC among distinct diagnostic subtypes of SM. Methods Overall, we studied 115 SM patients ‐ 45 bone marrow mastocytosis (BMM), 61 indolent SM (ISM), 9 aggressive SM (ASM)‐ and 32 healthy donors (HD). Spontaneous and in vitro‐stimulated cytokine production by blood monocytes, and their plasma levels, together with the distribution of different subsets of blood monocytes and DCs, were investigated. Results SM patients showed increased plasma levels and spontaneous production by blood monocytes of IL1β, IL6, IL8, TNFα and IL10, associated with an exhausted ability of LPS + IFNγ‐stimulated blood monocytes to produce IL1β and TGFβ. SM (particularly ISM) patients also showed decreased counts of total monocytes, at the expense of intermediate monocytes and non‐classical monocytes. Interestingly, while ISM and ASM patients had decreased numbers of plasmacytoid DC and myeloid DC (and their major subsets) in blood, an expansion of AXL+ DC was specifically encountered in BMM cases. Conclusion These results demonstrate an altered distribution of blood monocytes and DC subsets in SM associated with constitutive activation of functionally impaired blood monocytes and increased plasma levels of a wide variety of inflammatory cytokines, reflecting broad activation of the innate immune response in mastocytosis.

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Section: Discussionsupporting

confidence: 92%

supporting

confidence: 93%