Increased levels of eotaxin and MCP-1 in juvenile dermatomyositis median 16.8 years after disease onset; associations with disease activity, duration and organ damage.

Helga Sanner,Geir Christensen,Maria Vistnes,Berit Flatø,Ivar Sjaastad,Thomas Schwartz,Paul Proost

doi:10.1371/journal.pone.0092171

Abstract

ObjectiveTo compare cytokine profiles in patients with juvenile dermatomyositis (JDM) after medium to long-term follow-up with matched controls, and to examine associations between cytokine levels and disease activity, disease duration and organ damage.MethodsFifty-four JDM patients were examined median 16.8 years (2–38) after disease onset (follow-up) and compared with 54 sex- and age-matched controls. Cytokine concentrations in serum were quantified by Luminex technology. In patients, disease activity score (DAS), myositis damage index (MDI) and other disease parameters were collected by chart review (early parameters) and clinical examination (follow-up).ResultsSerum levels of eotaxin, monocyte chemoattractant protein-1 (MCP-1) and interferon-inducible protein 10 (IP-10) were elevated in JDM patients compared to controls (31.5%, 37.2% and 43.2% respectively, all p<0.05). Patients with active (n = 28), but not inactive disease (n = 26) had a higher level of MCP-1 than their respective controls. Levels of eotaxin and MCP-1 correlated with disease duration (r = 0.47 and r = 0.64, both p<0.001) and age in patients, but not with age in controls. At follow-up, MDI was associated with MCP-1(standardized β = 0.43, p = 0.002) after adjusting for disease duration and gender. High MDI 1 year post-diagnosis predicted high levels of eotaxin and MCP-1 at follow-up (standardized β = 0.24 and 0.29, both p<0.05) after adjusting for disease duration and gender.ConclusionPatients with JDM had higher eotaxin, MCP-1 and IP-10 than controls. High eotaxin and MCP-1 at follow-up was predicted by early disease parameters, and MCP-1 was associated with organ damage at follow-up, highlighting a role of these chemokines in JDM.

Highlights

Juvenile dermatomyositis (JDM) is a systemic autoimmune vasculopathy of childhood, involving proximal muscle weakness and characteristic skin lesions
Criteria for clinically inactive disease state in JDM were proposed by the Paediatric Rheumatology International Trials Organization (PRINTO) [10]; it is not clear whether disease state is associated with a specific signature of cytokines or inflammatory parameters
No differences were found between JDM-active and JDM-inactive in Erythrocyte sedimentation rates (ESR) (8.5 (6.1) vs 5.9 (4.7) mm, p = 0.09), C-reactive protein (CRP) (2.7 (2.8) vs 1.8 (3.7) mg/L, p = 0.36) or in the 29 cytokines studied (Table 2)

Summary

Introduction

Juvenile dermatomyositis (JDM) is a systemic autoimmune vasculopathy of childhood, involving proximal muscle weakness and characteristic skin lesions. Cytokines are small signal molecules, produced by endothelialimmune- and muscle cells. They mediate and regulate innate and adaptive immune responses and inflammatory reactions through a number of mechanisms including recruitment and activation of leukocytes [4]. Most studies performed on cytokines consist of mixed patients groups with polymyositis (PM), adult dermatomyositis (DM) and juvenile DM and if controlled, the studies are small. In a controlled study on 37 DM and 19 JDM patients (median disease duration 2 years), several chemokines including monocyte attractant protein-1 (MCP-1) and interferon-inducible protein 10 (IP-10) were increased [9]. Criteria for clinically inactive disease state in JDM were proposed by the Paediatric Rheumatology International Trials Organization (PRINTO) [10]; it is not clear whether disease state is associated with a specific signature of cytokines or inflammatory parameters

Methods

Results

Conclusion