2.1. Patients, controls and samples

A total of 115 SM patients diagnosed according to the WHO criteria 2 at the reference centres of the Spanish Network on Mastocytosis (REMA; Mast Cell Unit, Hospital del Valle, Toledo; and, Cancer Research Centre, Salamanca, Spain), were studied. Those included 45 BMM, 61 ISM and 9 ASM cases. Thirty‐two age‐matched healthy adult donors (HD) who had no past or present history of allergy or other immune disorders, were studied as controls. Demographic, biochemical and clinical data on SM patients grouped according to the diagnostic subtype of the disease are shown in Table 1 in Supplementary Information and their distribution per each set of assays performed is detailed in Table 2 in Supplementary Information. Briefly, functional analysis of spontaneous (ex vivo) cytokine production was initially investigated at the single‐cell level in 53 patients −20 BMM, 28 ISM and 5 ASM‐ and 16 HD; further in vitro monocyte‐stimulatory assays were performed in a subset of 7 of these 53 patients −2 BMM, 4 ISM and 1 ASM‐ and 15 HD. Quantification of cytokine plasma levels was performed in parallel in 52 patients −19 BMM, 28 ISM, and 5 ASM‐ and 6 HD‐ and flow cytometry immune cell profiling studies were done in 70 patients −24 BMM, 39 ISM and 7 ASM‐ and 12 HD; finally, soluble plasma levels of CCL2 (C‐C motif chemokine ligand‐2) and EMR2 plus CXCR2 (C‐X‐C motif chemokine receptor‐2), SAA1 (serum amyloid‐A1) and TLR2 (Toll Like Receptor‐2) were evaluated in 57 ‐20 BMM, 32 ISM and 5 ASM‐ and in 30 patients −9 BMM, 17 ISM and 4 ASM‐, respectively.

Each patient and HD gave his/her written informed consent to participate in the study according to the Declaration of Helsinki. The study was approved by the local Ethics Committees (approval codes: PI 2019 03 260 and CEIC 2016 09 07).