Ca V3.2 links mast cells, tryptase and pain
نویسندگان
چکیده
Abstract Hereditary a-tryptasemia (HaT) is a genetic trait defined by elevated serum tryptase caused increased TPSAB1 copy number and associated with multiple phenotypes including pain. CACNA1H encoding the voltage-gated calcium channel Ca V3.2 overlaps locus where partial gain-of-function (GOF) haplotype containing 3 linked variants has been shown to be co-inherited HaT in ~2/3 of individuals. While expressed neurons it contributes pain perception, expression also observed other cells. Mast cells are principal source tryptase, exist proximity nerves, have implicated sensation. We set out investigate links between these variants, mast cells, Performing genotyping via ddPCR cohort fibromyalgia patients we found that was enriched compared general population (p=0.029). However, universally present, suggesting were driving association. In support this observation, enrichment GOF among those without HaT. Using flow cytometry, immunoblotting, ddPCR, immunofluorescence, LAD2 express co-localizes at cell surface calnexin confirmed primary cultured human To our knowledge, first report on flux critical for activation, mechanisms activation remain elucidated. Future studies will help unravel linking pathways enabling development therapies commonly clinical phenotypes. Supported grant from DIR NIAID NIH, grant: ZIA AI001192
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.151.07