Session Title: Pediatric Rheumatology – Pathogenesis and Genetics Poster
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Interferons (IFNs) seem to be important contributors in the pathogenesis of juvenile dermatomyositis (JDM). Our group previously reported that expression of both type I and type II IFNs is increased in muscle biopsies of JDM patients and correlates with histological and clinical aspects of the disease, and other authors described up-regulation of interferon regulated genes (IRGs) in blood samples of JDM patients. The aim of this study was to investigate expression of IRGs (measured as type I IFN score) and serum levels of two type II IFN (IFNγ) induced chemokines (CXCL9, CXCL10) in peripheral blood of JDM patients. Furthermore, we wanted to evaluate possible correlations of type I IFN score, as well as of CXCL9 and CXCL10, with clinical and laboratory findings during disease course.
Methods: We collected 79 blood samples from 26 JDM patients at different times during the disease course. We measured expression of IRGs (IFI27, IFI44L, IFIT1, ISG15, RSAD2, SIGLEC1) by real-time PCR and calculated a type I IFN score; serum levels of CXCL9 and CXCL10 were analyzed by ELISA. The first blood sample was collected at the same time the patient underwent muscle biopsy in six patients. 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 and damage score, Childhood Myositis Assessment Score (CMAS), serum levels of creatine phosphokinase (CK, IU/l), prednisone (or equivalent) dose (mg/kg/daily), ongoing immunosuppressive medications.
Results: Blood expression levels of IRGs were up-regulated in untreated JDM patients at diagnosis compared to healthy controls. Type I IFN score progressively reduced after start of glucocorticoid and immunosuppressive therapy. CXCL9 and CXCL10 serum levels had a similar trend. These patients also showed an increased expression of IRGs, CXCL9 and CXCL10 in muscle biopsies obtained at diagnosis. We found that the type I IFN score correlates with cutaneous disease activity assessed by the CAT activity score (p = 0.027), whereas there was no significant correlation with cutaneous VAS (p = 0.09) or CAT damage score (p = 0.88). Serum levels of CXCL10 showed correlation with serum CK levels (p = 0.042) and muscular function assessed by CMAS (p = 0.021). None of the evaluated clinical features showed correlation with serum levels of CXCL9.
Conclusion: Our findings indicate that in addition to CXCL10, already suggested as potential biomarker in JDM, expression of IRGs measured as type I IFN score reflects disease activity in JDM.
To cite this abstract in AMA style:Nicolai R, Moneta GM, Caiello I, Pires Marafon D, Rosina S, Bracci Laudiero L, Ravelli A, De Benedetti F. Correlation of Type I Interferon Score and CXCL10 (C-X-C Motif Chemokine Ligand 10) with Cutaneous and Muscular Disease Activity in Juvenile Dermatomyositis Patients [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/correlation-of-type-i-interferon-score-and-cxcl10-c-x-c-motif-chemokine-ligand-10-with-cutaneous-and-muscular-disease-activity-in-juvenile-dermatomyositis-patients/. Accessed June 1, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/correlation-of-type-i-interferon-score-and-cxcl10-c-x-c-motif-chemokine-ligand-10-with-cutaneous-and-muscular-disease-activity-in-juvenile-dermatomyositis-patients/