Neutrophil gelatinase-associated lipocalin levels are associated with skin thickness and metabolic syndrome features in patients with systemic sclerosis.

Objectives: Systemic sclerosis (SSc) is a chronic multisystem disease characterised by microcirculatory vascular dysfunction and progressive fibrosis of the skin and internal organs. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein primarily secreted by immune cells and is known to be elevated in inflammatory states. Our study aims to investigate whether serum NGAL levels differ between individuals with SSc and healthy controls, and to explore its relationship with a comprehensive characterisation of disease features in SSc patients.

Methods: A cross-sectional study was conducted that included 81 individuals with SSc and 76 healthy age- and sex-matched controls. A multivariable analysis using linear regression was performed to determine whether NGAL serum levels differ between patients and controls, and to examine the relationship between NGAL levels and disease characteristics.

Results: Serum levels of NGAL do not differ significantly between patients and controls (188±110 vs. 197±147 ng/ml, p=0.67). However, after multivariable analysis, extension of the skin involvement (beta coefficient 5 [95% confidence interval 0.5-10] ng/ml, p=0.030) and disease duration (beta coefficient 6 [95% CI 0.1-12] ng/ml, p=0.045) were significantly associated with higher NGAL levels. Additionally, in patients with SSc, NGAL levels were independently and significantly related to a dyslipidaemia pattern manifested by higher serum levels of several lipid profile markers, such as LDL: HDL cholesterol ratio, apolipoprotein B: apolipoprotein A1 ratio, and atherogenic index. Furthermore, a significant and negative association between NGAL and the Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-S%) was found.

Conclusions: NGAL serum levels in patients with SSc correlate positively and independently with extension of the skin involvement. NGAL levels also correlate with features of metabolic syndrome, such as a dyslipidaemic pattern and reduced insulin sensitivity, which may be associated with an increased risk of atherosclerosis and cardiovascular disease in patients with SSc.