Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma

Kelsey E Magee,Katherine L Kurzinski,Kathryn S Torok,Jonhan Ho,Carol A Feghali-Bostwick,Christina E Kelsey,Logan R Mlakar

doi:10.1186/ar4378

Abstract

IntroductionThe purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures.MethodsThe presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC).ResultsIP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control.ConclusionsElevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS.

Highlights

The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures
Scleroderma, a connective tissue disease characterized by cutaneous sclerosis, is a broad term that encompasses both forms of the disease: systemic sclerosis (SSc) and localized scleroderma (LS), known as morphea
Blood sample and clinical data collection of LS patients was performed through the National Registry of Childhood Onset Scleroderma (NRCOS) which has been approved by the University of Pittsburgh Institutional Review Board (IRB) since 2003

Summary

Introduction

The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. LS, which is more prevalent in children, is characterized by sclerosis that is typically limited to the skin, subcutis, and underlying bone and tissue without vascular or internal organ involvement Both SSc and LS share a common underlying pathophysiology of excessive production and deposition of collagen and sclerosis in an autoimmune setting, they are clinically different with unique morbidities and prognoses. LS has Though the dermatopathology of these entities is similar and sometimes difficult to differentiate, there are a few characteristics which dermatopathologists document as occurring more frequently in LS compared to SSc, such as more overlying epidermal atrophy, more intense inflammation and more diffuse dermal sclerosis [2] Both LS and SSc share findings of an earlier active disease phase with newer lesions demonstrating a lymphocytic infiltrate with a variable number of plasma cells and eosinophils [2]. Inflammation density decreases as collagen bundles thicken and skin sclerosis increases in the later fibrotic phase of the disease [2]

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