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Epigenetic, transcriptional, and functional characterization of myeloid cells in familial Mediterranean fever

iScience, 2024

Röring R., Li W., Liu R., Bruno M., Zhang B., Debisarun P., Gaal O., Badii M., Klück V., Moorlag S., van de Veerdonk F., Li Y., Joosten L., Netea M.

Disease areaApplication areaSample typeProducts
Immunological & Inflammatory Diseases
Pathophysiology
Plasma
Cell Culture Supernatant
Olink Target 96

Olink Target 96

Abstract

Familial Mediterranean Fever (FMF) is a periodic fever syndrome caused by variation in MEFV. FMF is known for IL-1β dysregulation, but the innate immune landscape of this disease has not been comprehensively described. Therefore, we studied circulating inflammatory proteins, and the function of monocytes and (albeit less extensively) neutrophils in treated FMF patients in remission. We found that monocyte IL-1β and IL-6 production was enhanced upon stimulation, in concordance with alterations in the plasma inflammatory proteome. We did not observe changes in neutrophil functional assays. Subtle differences in chromatin accessibility and transcriptomics in our small patient cohort further argued for monocyte dysregulation. Together, these observations suggest that the MEFV-mutation-mediated primary immune dysregulation in monocytes leads to chronic inflammation that is subsequently associated with counterregulatory epigenetic/ transcriptional changes reminiscent of tolerance. These data increase our understanding of the innate immune changes in FMF, aiding future management of chronic inflammation in these patients.

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