Background: Growth differentiation factor 15 (GDF-15) is an inducible peptide with cardioprotective functions, whose expression is increased during hypoxia or oxidative stress conditions, such as ischemic myocardial injury (MI). It has been demonstrated to deter polymorphonuclear infiltration to the myocardium, and ultimately to counterbalance pathologic myocardial remodelling and fibrosis. A meta-analysis with over 53,000 patients highlighted its role as a useful prognostic biomarker for both hospitalization due to heart failure, and death due to cardiovascular disease. In lupus animal models, GDF-15 has been shown to negatively modulate immune cell activation, including plasma cell expansion and the induction of a type I interferon signature. However, the role of GDF-15 in human systemic lupus erythematosus (SLE) has not been addressed.

Objectives: To evaluate the plasma levels of GDF-15 in a cross-sectional cohort of SLE patients in comparison to population controls (PC), and to determine which clinical characteristics, within SLE patients, were associated with increased GDF-15 levels.

Methods: GDF-15 levels were measured by a commercially available ELISA kit (R&D # DY957) on plasma samples from the Karolinska SLE cohort (SLE n= 303, PC n= 303). The 95 ^th percentile of the PC measurement was established as a cut-off for dichotomous evaluation of high versus low levels. Statistical analysis was performed on SPSS v.29. Mann-Whitney, Spearman’s correlation, and Fisher exact tests were applied.

Results: Plasma levels of GDF-15 were elevated in SLE patients as compared to PC, with a mean GDF-15 level of 201 pg/mL in SLE, and a mean GDF-15 level of 161 pg/mL in PC (p=0.0016). Among SLE patients, GDF-15 levels were particularly increased in patients with a history of arterial events (p<0.0001), MI (p=0.03), and lupus nephritis (LN, p=0.004). Plasma levels above the 95 ^th percentile (239 pg/mL) were twice more frequent in LN (25.2% versus 12.7% of SLE patients without LN, p=0.006), and a moderate correlation between creatinine and GDF-15 plasma levels was observed (r _s = 0.418, p<0.001).

Conclusion: GDF-15 plasma levels are positively associated with a past of arterial events in general, and MI in particular, in SLE patients. Further, GDF-15 levels correlate with plasma creatinine levels, being primarily increased in patients with a history of LN.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.