Growth differentiation factor-15 as a potential biomarker in subclinical inflammation in familial mediterranean fever
Osman Cure1, Merve Huner Yigit2, Hakki Uzun3
1Department of Rheumatology, Faculty of Medicine, Recep Tayyip Erdogan University, 53000, Rize, Türkiye. osman.cure@erdogan.edu.tr.
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.
Insights
Growth Differentiation Factor-15 (GDF-15) is elevated in familial Mediterranean fever (FMF) patients during attack-free periods, indicating potential for subclinical inflammation assessment. This biomarker may help monitor low-grade inflammatory activity in FMF.
Area of Science:
- Biochemistry
- Immunology
- Genetics
Background:
- Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder characterized by recurrent inflammatory attacks.
- Assessing subclinical inflammation during the attack-free (intercritical) period is crucial for understanding disease burden.
- Growth Differentiation Factor-15 (GDF-15) is a stress-induced cytokine with potential roles in inflammation.
Purpose of the Study:
- To investigate GDF-15 as a potential biomarker for subclinical inflammation in FMF patients during intercritical periods.
- To compare GDF-15 levels between FMF patients and healthy controls.
- To explore the correlation of GDF-15 with inflammatory markers and MEFV mutations.
Main Methods:
- A case-control study involving 52 FMF patients in the attack-free period and 52 healthy controls.
- Serum GDF-15 levels were measured using ELISA.
- Acute-phase reactants (CRP, ESR, SAA, fibrinogen) and hematologic inflammation indices were evaluated.
- Statistical analyses included Mann-Whitney U, chi-square, Kruskal-Wallis, Spearman correlation, and ROC curve analysis.
Main Results:
- Serum GDF-15 levels were significantly higher in FMF patients compared to controls (p < 0.001).
- Subclinical inflammation (SAA > 10 mg/L) was present in 78.8% of FMF patients.
- GDF-15 positively correlated with CRP and SAA (p < 0.05).
- GDF-15 levels were higher in patients with subclinical inflammation and showed significant discriminative ability (AUC = 0.78 for FMF vs. controls, AUC = 0.74 for subclinical inflammation).
Conclusions:
- GDF-15 may serve as a valuable biomarker for reflecting persistent subclinical inflammation in FMF patients during intercritical periods.
- Elevated GDF-15 levels suggest ongoing low-grade inflammatory activity, potentially complementing conventional markers.
- GDF-15 levels did not significantly vary across different MEFV mutation subgroups or M694V status.
