Background/Purpose: Systemic sclerosis (SSc) is an intractable, connective tissue disease that causes fibrosis of the skin and organs and its prognosis is affected by pulmonary arterial hypertension (PAH). SSc presents with Raynaudfs phenomenon as the initial set of symptoms and is often accompanied by nailfold capillary abnormality. SSc is thought to cause microvascular disorder from the early stage. The chitinase-like protein YKL-40 has been implicated in inflammation, tissue remodeling, and angiogenesis in malignant tumors. A previous study in our department demonstrated elevated blood levels of YKL-40 in Japanese SSc patients. Globally, there are no reports examining the relationship between YKL-40 and vascular endothelial growth factor (VEGF) in SSc patients. Immunohistochemical (IHC) staining has not shown a relationship between YKL-40 and SSc in detail. We examined the relationship between YKL-40 and VEGF, which has an important role in angiogenesis.

Methods: We conducted a retrospective analysis of 84 SSc patients who were referred to our institution for treatment between August 2014 and April 2017. We excluded infection and malignant tumor complications. Controls were 15 healthy individuals. We measured serum YKL-40 levels and VEGF levels by ELISA and examined the correlation between YKL-40 age percentile, which was age-corrected for serum YKL-40 levels, and VEGF levels. Additionally, skin biopsy tissues from 7 SSc patients and 7 healthy individuals were also subjected to IHC staining with anti YKL-40 antibody.

Results: Our patient group included 11 men and 73 women with a mean age of 63.1 } 13.4 years and a mean disease duration of 9.6 } 9.8 years. The modified Rodnan total skin thickness score was 6.4 } 6.9. Diffuse cutaneous SSc was identified in 20 patients; limited cutaneous SSc was identified in the other 64 patients. The 15 healthy individuals included 2 men and 13 women with a mean age of 59.7 } 14.7. YKL-40 age percentile and VEGF levels in SSc patients (56.3 } 30.2 and 410.0 } 307.3 pg/ml, respectively) were significantly higher than in healthy individuals (24.9 } 17.4 and 295.0 } 154.5 pg/ml, respectively). The correlation coefficient (0.41) showed a mild correlation between YKL-40 age percentile and VEGF levels in SSc patients. Furthermore, staining of the blood vessel wall of the superficial dermis was found in specimens obtained from all SSc patients.

Conclusion: YKL-40 appears to reflect regeneration after capillary injury in SSc patients, with capillary vessels of the superficial dermis staining with IHC. There is a correlation between serum YKL-40 and VEGF levels in SSc patients.