Background/Purpose: Systemic sclerosis (SSc) is a chronic systemic disease characterized by skin and internal organs fibrosis along with vasculopathy. Previous studies have reported increased cadherin-11 (Cad11) levels in skin of SSc patients and identified Cad11 as a mediator of skin and lung fibrosis. The aim of this study is to determine if circulating Cad11 levels are increased in SSc patients as compared to healthy controls.

Methods: 300 SSc patients with early SSc enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) were studied. All patients fulfilled the ACR/EULAR for SSc and had disease duration < 5 years at the time of enrollment. Baseline or the earliest available serum samples from SSc patients were compared to 153 healthy controls matched for age, gender and race. Serum Cad11 levels were determined by ELISA. Sera with Cad11 levels above the lowest test standard in the ELISA (156 pg/ml) were considered positive for Cad11. Categorical variables were analyzed using the Chi-square method and the Fisher’s Exact Test. P value of <0.05 was considered significant.

Results:

SSc patients were enrolled with the median age of 50.1+/-13.1 years of which 83% were females. Average disease duration was 3.9 +/- 2.9 year. 42% of patients had limited SSc and 57% had diffuse SSc. SSc-associated autoantibodies were positive for anti-centromere (ACA) in 14%, for anti-topoisomerase (ATA) in 16% and anti-polymerase III (POLIII) in 22% of patients.

SSc patients had increased levels of serum Cad11 (574.8 +/- 140.7 pg/ml) compared to healthy controls (80.1 +/- 45.1 pg/ml). Serum Cad11 levels were above the lower limit of detection of the ELISA in 16.1% of SSc patients compared to 4.6% of controls. SSc patients were more likely to have detectable levels of serum Cad11 than controls (OR 4.1, 95%CI 1.9-8.8), which remained significant after adjusting for age, gender and race. Compared to patients with limited SSc, patients with diffuse SSc were less likely to have detectable levels of Cad11 in serum samples (limited 24%, diffuse 14%, OR 0.5, 95% CI 0.3-0.9). Chi squared analyses comparing ACA, ATA, and POLIII positivity did not reveal any differences between the autoantibody positive subsets or between the autoantibody positive subset versus the autoantibody negative subsets. Compared to healthy controls, the ACA+ and POLIII+ patients were more likely to have detectable Cad11 levels (p value 0.0006 and 0.027 respectively

Conclusion:

SSc patients are more likely to have detectable levels of serum cadherin-11 compared to healthy controls. These data add to the paradigm that suggests an important role for cadherin-11 in systemic sclerosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-circulating-cadherin-11-levels-in-patients-with-systemic-sclerosis/