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• W4220990803 abstract "The autoinflammatory disease familial Mediterranean fever (FMF), characterized by recurrent attacks of sterile fever, serosal, and/or synovial inflammation, is caused by variants in the Mediterranean fever gene, MEFV, coding for the pyrin inflammasome sensor. The diagnosis of FMF is mainly based on clinical symptoms and confirmed by detection of disease-associated MEFV variants. However, the diagnosis is challenging among patients carrying variants of uncertain clinical significance (VUS). In this study, we aimed to identify potential FMF discriminatory diagnostic markers in a cohort of clinically characterized FMF patients.We established a cohort of clinically and MEFV genotype-characterized FMF patients by enrolling patients from major Danish hospitals (n = 91). The secretory profile of pyrin inflammasome-activated monocytes from healthy donors (HDs) and MEFV-characterized FMF patients (n = 28) was assessed by analysing cell supernatants for a custom-designed panel of 23 cytokines, chemokines, and soluble tumour necrosis factor receptors associated with monocyte and macrophage function.MEFV genotypes in Danish FMF patients were associated with age at symptom onset (p < 0.05), FMF among relatives (p < 0.01), proportion of patients in colchicine treatment (p < 0.01), and treatment response (p < 0.05). Secretion of chemokines CCL1 and CXCL1 from pyrin-activated FMF monocytes was significantly decreased compared to HDs (p < 0.05), and could discriminate FMF patients with 'non-confirmatory' MEFV genotypes from HDs with 80.0% and 70.0% sensitivity for CCL1 and CXCL1, respectively (p < 0.05).Our data suggest that a functional diagnostic assay based on CCL1 or CXCL1 levels in pyrin-activated patient monocytes may contribute to FMF diagnosis in patients with VUS." @default.
• W4220990803 created "2022-04-03" @default.
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• W4220990803 date "2022-03-08" @default.
• W4220990803 modified "2023-09-26" @default.
• W4220990803 title "Monocyte secretory profiling in a clinical and MEFV genotype-characterized cohort of Danish familial Mediterranean fever patients: diagnostic potential of CCL1 and CXCL1." @default.
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• W4220990803 doi "https://doi.org/10.1080/03009742.2022.2028382" @default.
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