Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

Th1 and Th17 Cytokine Signatures in Early Pediatric Localized Scleroderma.

Torok3,  Kathryn S., Arkachaisri1,  Thaschawee, Medsger2,  Thomas A., Feghali-Bostwick4,  Carol A.

KK Women's and Children's Hosp, Singapore, Singapore
Univ of Pittsburgh, Pittsburgh, PA
Univ of Pittsburgh Med Ctr, Pittsburgh, PA
University of Pittsburgh, Pittsburgh, PA


Pediatric localized scleroderma (LS) is an autoimmune disease characterized by fibrosis of skin and underlying tissues, including subcutaneous tissue, tendons, and muscles. Infiltration of the skin with T cells is a key feature in both LS and systemic sclerosis (SSc). Specifically, T-helper (Th) cell subsets and their associated cytokines have been identified as contributing to the pathogenesis of scleroderma. Previous studies in both SSc and LS support a primary Th2 response, but more recent reports implicate the Th17 subset and associated cytokines. This study was designed to evaluate serum cytokines representative of all three Th cell lineages (Th1, Th2, Th17) in active pediatric LS.


Serum samples from 71 pediatric LS patients and 49 healthy pediatric controls were obtained. All of the LS patients had active disease, defined as having new lesion(s), expanding lesion(s) and/or erythematous skin lesion(s), and were naive to systemic medications. Two independent luminex assays were performed to evaluate the Th1, Th2, and Th17 serum cytokine profiles. Statistical analysis was completed using Wilcoxon-rank sum tests and chi-square tests with a p-value <0.05 as significant.


The ranks of the individual cytokines were not significantly different between LS patients and controls using Wilcoxon-rank sum tests. However, the p-value did trend toward significance (p = 0.05 – 0.30) with higher serum concentrations in the LS group for IL-1b, IL-6, IL-12p70, IL-17F, IL-22 and IFN-g. Among LS patients with a greater than 10-fold increase in one or more cytokine compared with the upper IQR level for that cytokine in healthy controls, there were correlations between individual cytokines and disease duration. High levels of IL-12p70, IFN-g, IL-1b, and IL-6 were significantly more frequently detected in LS patients with short disease duration (<24 months) compared with intermediate duration (24–48 months), who had elevated IL-17F and IL-22 levels, and those with long duration (>48 months), who had no elevated cytokine levels (p<0.05). Higher cytokine levels correlated with the presence of linear scleroderma, positive ANA, anti-ssDNA and anti-histone antibodies (p <0.05).


Th1 and Th17 related cytokines were elevated in the sera of pediatric LS patients with active disease with short to intermediate duration. Th1 associated cytokines appeared early and Th17 associated cytokines appeared later in disease course. Patients with greater elevations of these cytokines more often had linear LS, ss-DNA and anti-histone antibodies, all previously recognized predictors of more severe disease. Understanding and targeting the immune elements involved in the active early stages of LS is critical to designing novel therapies to prevent long-term complications such as thick fibrotic skin, loss of adipose tissue, joint contractures and limb-length discrepancies, which are associated with physical and psychological morbidity.

To cite this abstract, please use the following information:
Torok, Kathryn S., Arkachaisri, Thaschawee, Medsger, Thomas A., Feghali-Bostwick, Carol A.; Th1 and Th17 Cytokine Signatures in Early Pediatric Localized Scleroderma. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2006
DOI: 10.1002/art.29771

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