Serum calprotectin demonstrated significant potential as a novel biomarker for disease severity and activity in patients with systemic sclerosis (SSc), according to findings from a monocentric cross-sectional study published in the International Journal of Molecular Sciences. Conducted at a tertiary care center in Rome, the study assessed serum calprotectin levels in 74 consecutive SSc patients and compared them to 50 healthy controls using particle-based multianalyte technology (Aptiva).
In SSc patients, serum calprotectin levels showed a statistically significant positive correlation with the modified Rodnan skin score (mRSS) (r = 0.402, p < 0.001), disease activity index (DAI) (r = 0.420, p < 0.001), and disease severity scale (r = 0.365, p < 0.01). Conversely, there was a significant inverse correlation with pulmonary function parameters, including forced vital capacity (FVC) (r = -0.459, p < 0.001) and diffusion capacity for carbon monoxide (DLCO) (r = -0.445, p < 0.001). Notably, serum calprotectin levels were significantly higher in SSc patients with digital ulcers (DUs) [2.98 mcg/mL vs. 2.08 mcg/mL, p < 0.01] and those with interstitial lung disease (ILD) [2.56 mcg/mL vs. 1.96 mcg/mL, p < 0.01]. Multivariable stepwise logistic regression analysis confirmed calprotectin as independently associated with the presence of DUs (p < 0.05) and ILD [OR 3.687, 95% CI: 1.336–10.170, p < 0.05].
Calprotectin is a calcium-binding dimeric protein primarily found in the cytoplasm of neutrophils. It is actively secreted during immune activation or passively released during cell death and plays a central role in innate immune responses through Toll-like receptor signaling pathways. Due to its biochemical stability, calprotectin can also be measured in fecal samples (fecal calprotectin, F-cal), serving as a non-invasive biomarker of gastrointestinal mucosal inflammation, widely used in clinical practice.
In the context of SSc, elevated fecal calprotectin levels have been observed compared to healthy individuals and patients with other rheumatic conditions, including Sjögren’s syndrome and rheumatoid arthritis. Increased F-cal levels have been associated with gastrointestinal morbidity in SSc, suggesting a role in detecting subclinical or early GI tract involvement. A study by Marie et al. found that 74.4% of SSc patients had abnormal fecal calprotectin levels (>50 μg/g), with 54.4% exhibiting highly elevated levels (>200 μg/g). These levels correlated with digestive symptoms, esophageal dysfunction, and delayed gastric emptying. Similarly, Andréasson et al. demonstrated that fecal calprotectin levels in SSc patients remain stable over time and are significantly higher than in other autoimmune diseases, supporting its use in longitudinal monitoring of gastrointestinal involvement.
Collectively, these findings underscore the potential utility of calprotectin, both serum and fecal, as a biomarker for assessing disease burden and identifying patients at risk for severe complications, such as digital ulcers and ILD, in systemic sclerosis. Moreover, they pave the way for future research into calprotectin’s prognostic value and its integration into stratified therapeutic approaches for SSc management.
References
- Pellicano C, Villa A, Carnazzo V, D’Ippolito G, Vinante I, Laterza F, Basile U, Rosato E, Gigante A. Serum Calprotectin as a Novel Biomarker of Disease Severity and Activity in Systemic Sclerosis Patients. Int J Mol Sci. 2025 May 1;26(9):4290.
- Marie I, Leroi AM, Menard JF, et al. Fecal calprotectin in systemic sclerosis and review of the literature. Autoimmun Rev. 2015;14(6):547–554.
- Andréasson K, Saxne T, Scheja A, et al. Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjögren’s syndrome and rheumatoid arthritis. Arthritis Res Ther. 2014;16(1):R46
- Hamberg V, Wallman JK, Mogard E, Lindqvist E, Olofsson T, Andréasson K. Elevated fecal levels of the inflammatory biomarker calprotectin in early systemic sclerosis. Rheumatol Int. 2023 May;43(5):961-967.