Background SSc is a refractory of connective tissue disease that causes fibrosis of the skin and various organs. Recently, it is attention to 2013 ACR/EULAR classification criteria because can diagnose early phase before causing skin involvement in SSc. Thus, we considered that YKL-40 which is known to be involved in inflammation, tissue fibrosis and remodeling, is useful marker for evaluating early diagnosis and complications in SSc. YKL-40 is a chitinase-like protein and expressed in the synovial membrane and cartilage fibroblast cells in Rheumatoid Arthritis. Several cases of relationship between SSc and YKL-40 have been reported overseas, but it is unclear. Our report is the first in Japan.

Objectives We investigated serum YKL-40 levels and examined immunohistochemistry (IHC) with YKL-40 of cutaneous tissue in SSc patients. To clarify YKL-40 is useful biomarker in early diagnosis in the presence or absence of complications in Japanese SSc patients.

Methods Between August 2014 and March 2016, we treated 57 SSc patients in our department. We excluded infection, malignant disease, and other active complication may be a factor that increases YKL-40 levels. The patients were divided into 4 groups depending on whether suffered IP or PAH, which can affect the prognosis. Group1 (n=30) did not suffer from either IP or PAH, Group2 (n=12) suffered from IP, Group3 (n=7) suffered from PAH, and Group4 (n=8) suffered from both IP and PAH. YKL-40 levels in 4 groups and a control group of healthy individuals (n=13) were measured by ELISA. And age percentile strata of YKL-40 were calculated because serum YKL-40 levels have reported to rise with age; YKL-40 age percentile = 100/(1 + (Serum YKL-40 levels^-3) × (1.062^age) × 5000). IHC with YKL-40 of skin biopsy tissue from patients and controls was performed to investigate YKL-40 expression.

Results YKL-40 age percentile were elevated in Group1 compared to controls (42.0±24.5 vs 21.8±15.6), and were elevated due to complications (Group2, 3, 4: 61.8±21.4, 88.9±8.2, 94.4±8.7), with a tendency for PAH to cause greater elevation. There was no significant difference between Group3 and Group4, and a significant difference was found between the other groups (p<0.05). IHC with YKL-40 revealed staining of the vessels in the superficial dermis in SSc and normal skin remained unstained. The ROC curve for PAH showed an AUC=0.959, and the most valid cut-off levels of YKL-40 age percentile was 85.2 (sensitivity 86.7% and specificity 92.8%).

Conclusions Our report is the first report of IHC with YKL-40 in SSc. IHC suggest that YKL-40 may be further elevated by angiogenesis caused by microcirculatory damage in SSc. Our results suggest that YKL-40 may be very useful biomarker for diagnosing SSc and complications associated with microvascular lesions.

References

1. Cross-sectional evaluation of YKL-40 serum concentrations in patients with systemic sclerosis. Relationship with clinical and serological aspects of disease. La Montagna G, D'Angelo S, Valentini G. J Rheumatol. 2003;30(10):2147–51.

2. High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement. Nordenbaek C, Johansen JS, Halberg P, et al. Scand J Rheumatol. 2005;34(4):293–7.

3. Plasma YKL-40 levels in healthy subjects from the general population. Bojesen SE, Johansen JS, Nordestgaard BG. Clin Chim Acta 2011; 412(9–10): 709–12.

References

Disclosure of Interest None declared