Objectives Familial Mediterranean fever (FMF) is a multifaceted autoimmune disease and requires a diligent strategical approach considering disease periods and mutation subtypes. We aimed to investigate serum levels of autoimmunity-related cell-free miRNAs and inflammatory and apoptotic markers in FMF patients. Methods Sixty FMF patients, of which 30 were in attack (FMF-A) and 30 were in remission (FMF-R) periods, and 25 age-, sex-, and BMI-matched healthy controls were included in our study. The expression levels of miR-26a-5p, miR-146a-5p, miR-155–2-5p, and miR-451a were analyzed with reverse-transcriptase quantitative polymerase chain reaction, and protein levels of interleukin-18 (IL18) and soluble Fas cell surface death receptor (sFAS) were measured with enzyme-linked immunosorbent assay. Serum CRP levels were analyzed by nephelometry, ferritin levels by chemiluminescence, and routine biochemical parameters by spectrophotometry. Correlation analyses were performed to seek potential associations of miRNAs with serum markers and biochemical parameters. Potential biomarkers were tested with receiver operating characteristic analysis. Results We observed elevated serum IL18 levels but not sFAS, in FMF patients, particularly during attack period. IL18 demonstrated diagnostic value and was significantly correlated with acute-phase markers namely CRP, fibrinogen, and ferritin. Altered levels of IL18 and miR-451a could distinguish FMF patients in the attack period from the ones in remission. miR-26a-5p, miR-146a-5p, and miR-155–2-5p were downregulated in FMF patients carrying M694V mutations. Conclusions These findings suggest that IL18 and specific miRNAs can serve as potential biomarkers for FMF pathogenesis. Discovering promising targets for FMF-related miRNAs using mechanistic strategies will enhance our understanding of FMF disease management and therapy. <Table Float="No" ID="Taba"> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> Key Points </entry> </row> <row> <entry align="left" colname="c1"> • miR-451a and IL18 can serve as an indicator in distinguishing familial Mediterranean fever patients in attack and remission periods. • miR-26a-5p, miR-146a-5p, and miR-155–2-5p were dysregulated in FMF patients carrying M694V mutation. </entry> </row> </tbody> </tgroup> </Table>

miR-451a and IL18 can differentiate familial Mediterranean fever patients in attack and remission periods: a prospective cross-sectional study

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2025年2月11日

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Menderes Yusuf Terzi,
Oğuzhan Özcan,
Gezmiş Kimyon,
Hamza Malik Okuyan,
Abdullah Arpacı,
Serdar Doğan

摘要

Objectives

Familial Mediterranean fever (FMF) is a multifaceted autoimmune disease and requires a diligent strategical approach considering disease periods and mutation subtypes. We aimed to investigate serum levels of autoimmunity-related cell-free miRNAs and inflammatory and apoptotic markers in FMF patients.

Methods

Sixty FMF patients, of which 30 were in attack (FMF-A) and 30 were in remission (FMF-R) periods, and 25 age-, sex-, and BMI-matched healthy controls were included in our study. The expression levels of miR-26a-5p, miR-146a-5p, miR-155–2-5p, and miR-451a were analyzed with reverse-transcriptase quantitative polymerase chain reaction, and protein levels of interleukin-18 (IL18) and soluble Fas cell surface death receptor (sFAS) were measured with enzyme-linked immunosorbent assay. Serum CRP levels were analyzed by nephelometry, ferritin levels by chemiluminescence, and routine biochemical parameters by spectrophotometry. Correlation analyses were performed to seek potential associations of miRNAs with serum markers and biochemical parameters. Potential biomarkers were tested with receiver operating characteristic analysis.

Results

We observed elevated serum IL18 levels but not sFAS, in FMF patients, particularly during attack period. IL18 demonstrated diagnostic value and was significantly correlated with acute-phase markers namely CRP, fibrinogen, and ferritin. Altered levels of IL18 and miR-451a could distinguish FMF patients in the attack period from the ones in remission. miR-26a-5p, miR-146a-5p, and miR-155–2-5p were downregulated in FMF patients carrying M694V mutations.

Conclusions

These findings suggest that IL18 and specific miRNAs can serve as potential biomarkers for FMF pathogenesis. Discovering promising targets for FMF-related miRNAs using mechanistic strategies will enhance our understanding of FMF disease management and therapy.

Key Points

• miR-451a and IL18 can serve as an indicator in distinguishing familial Mediterranean fever patients in attack and remission periods.

• miR-26a-5p, miR-146a-5p, and miR-155–2-5p were dysregulated in FMF patients carrying M694V mutation.