Background/Purpose:
Localized scleroderma (LS) is an autoimmune disease of the skin and underlying tissues which results in disfigurement and orthopedic complications, especially when the onset is in childhood. LS has both inflammatory and fibrotic components, making it similar to systemic sclerosis (SSc), its ‘companion’ disease. Identifying potential biomarkers involved with disease propagation may lead to future therapeutic targets. T-helper (Th) cell subsets and their associated cytokines are thought to contribute to the pathogenesis of systemic sclerosis (SSc). Traditionally, a Th2 predominant response has been supported, but more recent data also implicate Th1, Th17 and various chemokine involvement. This concept in LS has only been partially investigated, with studies evaluating only a handful of cytokines associated with Th cell lineages, and not examined in reference to disease activity. This study was designed to extensively evaluate the Th-cell associated plasma cytokine and chemokine profiles of patients with pediatric LS.

Methods:
Plasma samples were obtained from 69 pediatric LS patients and 71 healthy pediatric controls. Twenty-nine cytokines and chemokines were analyzed using a Th1, Th2, and Th17 Millipore luminex panel comparing LS to healthy controls, with additional analyses predetermined to be dedicated to disease activity parameter. The modified Localized Scleroderma Severity Index (mLoSSI) and the Physician Global Assessment of Disease Activity (PGA-A) were the main parameters compared to the cytokine/chemokine levels. Mann-Whitney U test was employed to compare cytokine levels between LS and healthy groups and Spearman rank correlation was used to determine relationships between individual analytes and clinical parameters (p <0.05). Type I error due to multiple testing was controlled for using the Benjamini-Hochberg method.

Results:
The levels of the following cytokines were significantly elevated in LS patients compared with healthy controls: IP-10, MCP-1, IL-17A, IL-12p70, GM-CSF, IFN-γ, IFN-α2 and PDGF-bb. When LS patients were further divided into active (n=30) and inactive states (n=39), IP-10 was significantly elevated in the active group compared to inactive (median: 2087.3 vs. 880.5 pg/ml, respectively). IP-10 levels were also significantly correlated with the Physician Global Assessment of Disease Activity (PGA-A) score (rs = 0.450, p = 0.005) and with the modified Localized Scleroderma Severity index (mLoSSI) score (rs = 0.343, p = 0.004).

Conclusion:
SSc and LS share a similar histopathology with infiltration of lymphocytes and their associated effector cytokines in skin specimens. In the current study we demonstrated a serological presence of IP-10, MCP-1, IL-17A, IL-12p70, GM-CSF, IFN-γ and IFN-α2 in localized scleroderma, with IP-10 being highly correlated with active disease. Prior SSc studies have also found similar cytokine and chemokine profiles in the circulation, with recent literature supporting a potential role of IP-10 in SSc disease severity. These findings suggest a potential immunological link between these two clinically different diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-t-helper-cell-associated-cytokines-and-chemokines-in-localized-scleroderma/