IFN Level Assessed By Ultrasensitive Detection Technology in Myositis Patient: A Promising Biomarker of Disease Activity in Dermatomyositis and Anti-Synthetase Syndrome

Loïs BOLKO^1,2, Ségolène Toquet³, Océane Landon-Cardinal⁴, Karim DORGHAM⁵, Celine Anquetil⁶, Darragh Duffy⁷, Nadège WESNER⁸, Damien Amelin⁹, Gaëlle DZANGUE TCHOUPOU², Perrine Guillaume¹⁰, Aude Rigolet¹¹, Baptiste Hervier¹¹, Mathieu Vautier¹¹, Nicolas Champtiaux¹¹, Guy Gorochov¹², Jean-Hugues Salmon¹³, Olivier Benveniste¹¹ and Yves Allenbach¹⁴, ¹Rheumatology, CHU Reims, Hôpital Maison Blanche, Reims, France, ²INSERM UMRS974, Pitié-Salpêtrière University Hospital, Paris, France, ³Médecine interne, CHU Reims, Robert debré, Reims, France, ⁴Rhumatologie, Hopital Notre-Dame Montréal, Montreal, QC, Canada, ⁵CIMI, INSERM, Paris, France, ⁶CDR en myologie UMR974,, Institut National de la Santé et de la Recherche Médicale, Association Institut de Myologie, PARIS, France, ⁷Institut Pasteur, Paris, Paris, France, ⁸INSERM UMRS974, Pitié-Salpêtrière University Hospital, paris, France, ⁹Sorbonne Universités UPMC Univ Paris 06, Myology research center, INSERM UMRS974, CNRS FRE3617, Pitié-Salpêtrière University Hospital, Paris, France, Paris, France, ¹⁰Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Universitaire Pitié Salpêtrière, paris, France, ¹¹Department of Internal Medicine and Clinical Immunology and Inflammation-Immunopathology-Biotherapy Department (I2B), Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, East Paris Neuromuscular Diseases Reference Center, Paris, France, ¹²CIMI, INSERM, paris, France, ¹³Service de Rhumatologie, CHU Reims, Hôpital Maison Blanche, Reims, France, ¹⁴Internal Medicine and Clinical Immunology, Sorbonne University - Assistance Public - Hopitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Biomarkers, interferons, Myositis and outcome measures

Session Information

Date: Sunday, October 21, 2018

Title: 3S084 ACR Abstract: Muscle Biology, Myositis & Myopathies I: Biomarkers (875–879)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

Inflammatory idiopathic myopathies (IIM) is a heterogeneous group of disorders ranging from muscle specific auto-immune diseases to systemic ones (dermatomyositis (DM), anti-synthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM) and inclusion body myositis (IBM)). Recent insight into DM pathogenesis highlighted the role of type I interferon (IFN) and the level of IFN-pathway activity is linked to those of the disease.

The aim of this study was to measure IFN-a seric level in the different groups of myositis using an ultrasensitive detection technology to evaluate IFN-α as disease activity biomarker.

Methods:

IIM patients were enrolled in a monocentric prospective cohort. Clinical and biological data were prospectively collected as well as sera and peripheral blood mononuclear cells. Disease activity was assessed by calculating the Physician Global Activity (PGA) for each patient. To measure IFN-α level, sera were analyzed by single molecule array technology (SIMOA). The expression of IFN-stimulated genes (ISG) was detected by quantitative RT-PCR assays, and IFN scores were asses by the median gene expression of the 5(ISG).

Results:

One hundred and sixty-four patients (57 DM, 48 ASS, 35 IMNM and 24 IBM) and 35 age- and sex-matched healthy controls were included. Patient’s characteristics were similar in all groups, but IBM patients were older (67.5 [63.5-78]) with a more severe weakness (Manual muscle testing 8 score was 120±19) compared to DM (142±7.6, p=0.001) and to ASS patients (148±12.4, p<0.001).

IFN-α levels were higher in DM (0.05±1.3 pg/ml, p=0.005) and ASS groups (0.06±0.2 pg/ml, p=0.005) compare to controls (0.02±0.06 pg/ml). IFN-α levels were similar in IMNM (0.03±0.11 pg/ml), IBM (0.02±0.07 pg/ml) and controls groups. As expected, anti-Jo1 antibody was associated with higher IFN-a level (p=0.05). IFN-α levels were correlated to disease activity in DM (r=0.72, p<0.0001) and ASS groups (r=0.47, p=0.0009).

Active (PGA>5) DM patients had a higher level of IFN-α (0.28±1.9 pg/ml) compared to non-active patients (0.03±0.05 pg/ml, p<0.001) and controls (0.02±0.06 pg/ml; p<0.001). The accuracy of IFN-α level to discriminate active and non-active disease was excellent attested by an area of 0.92 under the ROC-curve (AUC). For an IFN-α level above 0.15 pg/ml, the sensitivity was 72.7% and specificity was 96.4%. Active ASS patients had also higher IFN-a level (0.16±0.26 pg/ml) compare to non-active patients (0.04±0.1 pg/ml, p=0.003) and controls (p<0.001). In ASS group, the accuracy of the test was also good (AUC=0.80) but the sensitivity and specificity were lower (52% and 87% respectively) for an IFN-a level cut-off at 0.29 pg/ml.

In naïve DM and ASS patients (n=12), IFN scores, considered as the gold standard to measure IFN activation, were assessed. The correlation between IFN score and IFN-α levels was very good (r=0.76, p=0.005).

Conclusion:

IIM IFN-α level (assessed by SIMOA) is increased not only in DM but also in ASS patients. It is strongly correlated with disease activity especially in DM patients showing that it can be considered as biomarker of disease activity.

Disclosure: L. BOLKO, None; S. Toquet, None; O. Landon-Cardinal, None; K. DORGHAM, None; C. Anquetil, None; D. Duffy, None; N. WESNER, None; D. Amelin, None; G. DZANGUE TCHOUPOU, None; P. Guillaume, None; A. Rigolet, None; B. Hervier, None; M. Vautier, None; N. Champtiaux, None; G. Gorochov, None; J. H. Salmon, Novartis, 5,Janssen, 5; O. Benveniste, None; Y. Allenbach, None.

To cite this abstract in AMA style:

BOLKO L, Toquet S, Landon-Cardinal O, DORGHAM K, Anquetil C, Duffy D, WESNER N, Amelin D, DZANGUE TCHOUPOU G, Guillaume P, Rigolet A, Hervier B, Vautier M, Champtiaux N, Gorochov G, Salmon JH, Benveniste O, Allenbach Y. IFN Level Assessed By Ultrasensitive Detection Technology in Myositis Patient: A Promising Biomarker of Disease Activity in Dermatomyositis and Anti-Synthetase Syndrome [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/ifn-level-assessed-by-ultrasensitive-detection-technology-in-myositis-patient-a-promising-biomarker-of-disease-activity-in-dermatomyositis-and-anti-synthetase-syndrome/. Accessed .

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