Background/Purpose: Interferons (IFNs) seem to play an important role in the pathogenesis of juvenile dermatomyositis (JDM). We previously reported that expression of both type I and type II IFN related genes is increased in muscle biopsies of JDM patients and correlates with histological and clinical features of the disease. Interferon regulated genes (IRGs) have also been reported to be upregulated in peripheral blood of JDM patients and could represent valuable biomarkers of disease activity. The aim of this study was to investigate expression of IRGs (measured as type I IFN score), as well as serum levels of two type I and type II IFN induced chemokines (CXCL9, CXCL10) in peripheral blood of JDM patients and to assess their correlations with clinical and laboratory findings.

Methods: We collected 125 blood samples from 28 JDM patients at different time points during follow-up. We measured expression of IRGs (IFI27, IFI44L, IFIT1, ISG15, RSAD2, SIGLEC1) by quantitative PCR (qPCR) and calculated the type I IFN score; serum levels of CXCL9 and CXCL10 were analyzed by ELISA. At each visit, the following clinical data were recorded: physician’s global assessment of disease activity VAS (Visual Analogue Scale), cutaneous VAS, Cutaneous Assessment Tool (CAT) activity score, Childhood Myositis Assessment Score (CMAS), serum levels of creatine phosphokinase (CK, IU/l), antinuclear antibody (ANA) status, presence of myositis specific or myositis associated antibodies (MSA/MAA), prednisone (or equivalent) dose (mg/kg/daily) ongoing immunosuppressive medications.

Results: Type I IFN score was significantly higher in patients with features of active disease (physician’s global VAS >0.2, CAT activity score≥1, CK>150 IU/l). CXCL10 levels were significantly higher in patients with features of active muscle disease (CMAS<46, CK>150 IU/l) whereas CXCL9 levels were significantly higher only in patients with abnormal CK levels. In a multilevel mixed effect approach, type I IFN score was significantly associated with physician’s global VAS, cutaneous VAS, CAT activity score, CMAS and CK levels; CXCL9 showed no significant association with the evaluated clinical features; CXCL10 levels were significantly associated with CK levels and CMAS. Including time from disease onset to sampling did not change the results. Immunosuppressive medications negatively modulated expression of IRGs and IFN induced chemokines.

Conclusion: Our findings indicate that expression of IRGs, measured as type I IFN score, and serum levels of CXCL10 reflect specific features of disease activity in JDM, further supporting their role as valuable disease biomarkers.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/correlations-of-type-i-interferon-score-and-interferon-induced-chemokines-cxcl10-and-cxcl9-with-cutaneous-and-muscular-disease-activity-in-juvenile-dermatomyositis/