Objectives This study aimed to investigate whether growth differentiation factor-15 (GDF-15) can serve as a potential biomarker for assessing subclinical inflammation during the attack-free (intercritical) period in patients with familial Mediterranean fever (FMF). Methods In a single-center cross-sectional case–control study, 52 FMF patients in the attack-free period were compared with 52 age- and sex-matched healthy controls. ELISA measured serum GDF-15 levels; acute-phase reactants (CRP, ESR, SAA, fibrinogen) and various hematologic inflammation indices were evaluated. Statistical analyses included the Mann–Whitney U, chi-square, Kruskal–Wallis, Spearman correlation, and ROC curve methods. Results Serum GDF-15 levels were significantly higher in the FMF group than in controls (p < 0.001). Subclinical inflammation, defined by SAA > 10 mg/L, was detected in 78.8% of FMF patients. GDF-15 correlated positively with CRP and SAA (p < 0.05). GDF-15 levels did not differ across MEFV mutation subgroups or by the presence of the M694V mutation. Patients with subclinical inflammation had significantly higher GDF-15 levels than those without. ROC analysis showed that GDF-15 had a statistically significant ability to distinguish FMF from controls (AUC = 0.78; p < 0.001) and to identify subclinical inflammation (AUC = 0.74; p = 0.014). Conclusion GDF-15 appears to be a potential biomarker reflecting ongoing subclinical inflammation during the attack-free period in FMF. Elevated GDF-15 levels in patients with SAA-defined subclinical inflammation suggest that GDF-15 may reflect low-grade inflammatory activity. Larger studies are needed to validate these findings. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • Serum GDF-15 was significantly higher in the attack-free FMF patients than in controls, supporting its potential to reflect persistent low-grade (subclinical) inflammation. • GDF-15 showed moderate discriminative performance (AUC 0.783) and may complement conventional acute-phase reactants in assessing inflammatory burden during attack-free periods. • GDF-15 levels did not differ significantly across MEFV mutation subgroups or by M694V status in this cohort. </entry> </row> </tbody> </tgroup> </Table>

Growth differentiation factor-15 as a potential biomarker in subclinical inflammation in familial mediterranean fever

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2026年3月30日

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Osman Cure,
Merve Huner Yigit,
Hakki Uzun,
Huseyin Cinar Zihni,
Ertugrul Yigit

摘要

Objectives

This study aimed to investigate whether growth differentiation factor-15 (GDF-15) can serve as a potential biomarker for assessing subclinical inflammation during the attack-free (intercritical) period in patients with familial Mediterranean fever (FMF).

Methods

In a single-center cross-sectional case–control study, 52 FMF patients in the attack-free period were compared with 52 age- and sex-matched healthy controls. ELISA measured serum GDF-15 levels; acute-phase reactants (CRP, ESR, SAA, fibrinogen) and various hematologic inflammation indices were evaluated. Statistical analyses included the Mann–Whitney U, chi-square, Kruskal–Wallis, Spearman correlation, and ROC curve methods.

Results

Serum GDF-15 levels were significantly higher in the FMF group than in controls (p < 0.001). Subclinical inflammation, defined by SAA > 10 mg/L, was detected in 78.8% of FMF patients. GDF-15 correlated positively with CRP and SAA (p < 0.05). GDF-15 levels did not differ across MEFV mutation subgroups or by the presence of the M694V mutation. Patients with subclinical inflammation had significantly higher GDF-15 levels than those without. ROC analysis showed that GDF-15 had a statistically significant ability to distinguish FMF from controls (AUC = 0.78; p < 0.001) and to identify subclinical inflammation (AUC = 0.74; p = 0.014).

Conclusion

GDF-15 appears to be a potential biomarker reflecting ongoing subclinical inflammation during the attack-free period in FMF. Elevated GDF-15 levels in patients with SAA-defined subclinical inflammation suggest that GDF-15 may reflect low-grade inflammatory activity. Larger studies are needed to validate these findings.

Key Points

• Serum GDF-15 was significantly higher in the attack-free FMF patients than in controls, supporting its potential to reflect persistent low-grade (subclinical) inflammation.

• GDF-15 showed moderate discriminative performance (AUC 0.783) and may complement conventional acute-phase reactants in assessing inflammatory burden during attack-free periods.

• GDF-15 levels did not differ significantly across MEFV mutation subgroups or by M694V status in this cohort.