Background/Purpose: Juvenile systemic sclerosis (jSSc) is a severe and heterogeneous autoimmune vasculopathy. Pulmonary fibrosis is the highest independent predictor of mortality, yet currently there are no known biomarkers associated with organ involvement, response to therapy, or prognosis in jSSc. CXCL4 is a chemoattractant for neutrophils and fibroblasts. Elevated peripheral levels of CXCL4 have been associated with pulmonary fibrosis, pulmonary hypertension, and overall disease progression in adult SSc. The purpose of this study was to evaluate whether CXCL4 levels are elevated in jSSc patients as compared to healthy pediatric controls and patients with other rheumatologic illnesses, and to determine whether there is an association with jSSc disease manifestations.

Methods: In this multi-center case-control study, plasma samples from 28 patients with jSSc, 26 with localized scleroderma (jLS), 36 with juvenile systemic lupus erythematosus (jSLE), and 35 age-matched healthy controls were tested for CXCL4. Testing was done on a Luminex 200 luminometer (Eve Technologies, Calgary, AB). CXCL4 plasma concentration was compared between diseases and controls. The CXCL4 level was then correlated with specific disease manifestations, including the presence of pulmonary hypertension and pulmonary fibrosis on HRCT.

Results: The mean (± 95% CI) level of CXCL4 in jSSc patients was 24,358 ± 6047 ng per milliliter, which was significantly higher than in controls (12,455 ± 5032 ng/mL; p=.001). Mean CXCL4 in both jLS patients (20,692 ± 4513 ng/mL) and in jSLE (18,165 ± 4360 ng/mL) were also significantly higher than in controls, but to lesser extent (p=.01 and p=.04, respectively). When the Bonferroni correction was applied, only the jSSc cohort was significantly different from controls. There was no significant difference in CXCL4 level between the sub-classifications of jSSc (diffuse versus limited cutaneous SSc). Within the jSSc cohort, there were three patients with PH and a mean CXCL4 level of 41,768 ng/mL (range 3,472 – 79,585), compared to 24,565±19,731 ng/mL for 17 patients with pulmonary fibrosis, and 24,600±8,927 ng/mL for patients without cardiopulmonary involvement.

Conclusion: Levels of plasma CXCL4 were elevated in patients with jSSc and, in a small number of patients, were higher with the presence of pulmonary hypertension. Levels did not correlate with HRCT-confirmed pulmonary fibrosis in this cohort. These findings suggest that CXCL4 may have value as a biomarker in jSSc, but further prospective studies of an inception cohort are needed.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasma-cxcl4-as-a-biomarker-in-juvenile-systemic-sclerosis/