Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic sclerosis (SSc) is an intractable connective tissue disease that causes fibrosis of the skin and organs. The prognosis of this disease is affected by interstitial pneumonia (IP) and pulmonary arterial hypertension (PAH). Chitinase-like protein YKL-40 has been implicated in inflammation and tissue remodeling. A previous study in our department demonstrated elevated blood levels of YKL-40 in Japanese SSc patients. Examinations of the relationship between YKL-40 and PAH in SSc using immunohistochemistry (IHC) have yet to be reported in detail.
Methods: Subjects comprised 50 SSc patients without complications examined in our department between August 2014 and April 2017 (Group 1), 18 SSc patients with IP (Group 2), 5 SSc patients with PAH (Group 3), and 5 SSc patients with both IP and PAH (Group 4), as well as a control group of 17 healthy individuals (Group 0). IHC was performed on 7 samples of normal skin and 7 stored samples of SSc skin. Serum levels of YKL-40 were measured by Enzyme Linked Immuno Sorbent Assay and age-adjusted reference levels were calculated [age-percentile strata for YKL-40 = 100/(1+(YKL-40-3)×(1.062age)×5000)].
Results: We first examined Groups 0, 1 and 2. The YKL-40 age-percentile was 23.9±17.1 in Group 0, significantly higher than in Group 1 (46.3±26.6) or Group 2 (54.2±26.7) (Steel-Dwass test between Groups 0, 1 and 2, p<0.01). No significant difference was evident between Groups 1 and 2 (p=0.52). We then performed immunostaining with YKL-40 antibody for specimens from healthy individuals and SSc patients. All normal skin remained unstained by IHC, whereas subcutaneous vascular endothelium showed prominent staining in all SSc samples. Finally, we examined SSc patients with PAH. YKL-40 age-percentile was 89.7±10.4 in Group 3 and 94.0±11.2 in Group 4. No significant difference was seen between Groups 3 and 4 (Steel-Dwass test between Groups 1-4, p=0.63), or between Groups 1 and 2 (p=0.69)．A significant difference was found between the other groups (p<0.05). YKL-40 age-percentile was more increased with PAH than with other conditions. SSc patients were divided based on presence or absence of PAH and ROC analysis was performed. SSc complicated with PAH could be diagnosed with 80.0% sensitivity and 94.1% specificity.
Conclusion: YKL-40 appears to reflect regeneration from capillary injury in SSc, as capillary vessels of the superficial dermis showing staining under IHC. PAH may reflect angiogenesis due to capillary injury in SSc, along with significant rises in YKL-40 in Groups 3 and 4 that complicated PAH and IHC results. YKL-40 may offer a useful and easily applied diagnostic biomarker for SSc and complicated PAH.
To cite this abstract in AMA style:Furukawa T, Matsui K, Kitano M, Yokoyama Y, Azuma N, Sano H. Sensitivity and Specificity of YKL-40 for the Presence of Pulmonary Arterial Hypertension in Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/sensitivity-and-specificity-of-ykl-40-for-the-presence-of-pulmonary-arterial-hypertension-in-systemic-sclerosis/. Accessed November 22, 2017.
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