Background/Purpose: Patients with systemic sclerosis (SSc) display reductions in adipose tissue, particularly intradermal adipose tissue.  There are currently no well-validated serum biomarkers in SSc, and adipokines represent an attractive biomarker because of their roles in inflammation, vascular function, and fibrosis.  Previous studies have shown an association between circulating levels of the adipokine adiponectin and SSc, particularly in patients with diffuse cutaneous involvement (dcSSc).  This study sought to determine if adipokine profiles were associated with dcSSc and measures of SSc organ involvement.

Methods: 82 dcSSc patients and 35 healthy controls were included in the study.  All dcSSc patients underwent standard laboratory assessment, pulmonary function tests, and the modified Rodnan skin score (MRSS) within 6 months of the serum collection.  54 patients also had research quantitated echocardiograms within 6 months of serum collection.  Serum leptin, adiponectin, and adipsin levels were measured by luminex assays in all patients and controls.  Mann-Whitney U test and Kruskall-Wallis tests were used in binary between-group comparisons and testing of inter-group variability.

Results: Distributions of age, sex, and BMI in dcSSc patients and healthy controls were not different although a higher proportion of patients than controls were female (77% vs 58%, p=0.002).  Among patients, the mean disease duration was 3.6 years, 29% were Scl70 antibody positive, 44% were RNA polymerase III antibody positive, the mean MRSS was 18.5, the mean predicted forced vital capacity (FVC) was 75%, the mean echo-measured pulmonary artery systolic pressure was 33 mmHg, and 17% had diastolic dysfunction.

Adiponectin (4.3 vs 5.8 μg/ml, p=0.04) and adipsin (7.1 vs 9.0 pg/ml, p=0.001) levels in dcSSc patients were significantly lower than controls.  Low levels of adiponectin and adipsin were associated with decreased FVC (p=0.001, and p=0.02, respectively).  Patients also had an increased leptin/adiponectin ratio compared to controls (0.31 vs 0.26, p=0.004) and this ratio was associated with diastolic dysfunction (p=0.04) and left ventricular ejection fraction (p=0.05).  Leptin was not associated with disease, but among patients, there was an association between higher leptin levels and BMI (p=0.01) and diastolic dysfunction (p=0.01).  None of the adipokine levels were significantly associated with antibody status, disease duration, MRSS, or pulmonary artery pressure.

Conclusion: This study affirms the association of decreased adiponectin with dcSSc and finds new associations between decreased serum adipsin and an increased leptin/adiponectin ratio with dcSSc.  Adipokine profiles may be useful in assessing risk and monitoring cardiac and pulmonary manifestations of SSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-serum-adipokines-adipsin-adiponectin-and-leptinadiponectin-ratio-with-systemic-sclerosis/