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BackgroundIdiopathic inflammatory myopathies (IIM) or myositis are a group of rare autoimmune diseases that combine muscle weakness and multi-visceral damage. The discovery of IIM-specific autoantibodies (aAbs) and their associations with clinical phenotypes has improved diagnostic and classification criteria. Faced with the large number of these aAbs, multiplexed techniques have emerged. Among them, the immunodot is simple, rapid, and inexpensive, but has been several times criticized for its lack of specificity.ObjectivesOur objective was to evaluate the current interpretation criteria of the D-Tek immunodot and to propose new interpretation rules based on clinical criteria in order to improve its reliability.MethodsWere included in this retrospective study patients tested positive result on the semi-quantitative myositis/synthetase immunodots at manufacturer threshold (≥ 5 UA), for at least one of the 15 aAbs: anti-SRP, anti-NXP2, anti-TIF1, anti-SAE (1 and 2), anti-Mi2, anti-MDA5, anti-Jo1, anti-PL7, anti-PL12, anti-EJ, anti-OJ, anti-KS, anti-ZO, anti-HA. Specificity of the immunodots was further evaluated using 60 healthy and anonymous subjects (French blood bank, Toulouse, France). The clinical diagnosis and sub-classification retained by the clinician in charge of the patient was used as a reference for attribution to the myositis/non-myositis group and subgroups. For the myositis group, 7 subgroups were considered: immune-mediated necrotizing myopathy (n=4); dermatomyositis (n=66); anti-synthetase syndrome (n=36); inclusion body myositis (n=1); overlap myositis with another connective tissue disease (n=7); polymyositis (n=8); and unclassified myositis (n=6). For the non-myositis group, patients were subdivided in 4 subgroups: autoimmune or inflammatory diseases (n=72); isolated and diffuse interstitial lung disease (n=26) not associated with other myositis criteria; other non-inflammatory myopathies (n=8) including genetic, metabolic, and toxic myopathies; and other diseases (n=36). The immunodot interpretation thresholds were evaluated both in relation to the manufacturer’s threshold, and by considering the phenotypes and clinical diagnoses using a ROC method (Youden’s index).ResultsAmong 270 patients included between 01/07/2016 and 30/06/2020, 128 (47%) were classified as myositis (median age 58 years, 60% women, 52% DM and 28% AS) and 142 (53%) in non-myositis. Among the 15 aAbs analyzed, none were detected in the healthy control group but they were represented in both myositis and non-myositis group. Among them only 2 (anti-Jo1, anti-Mi2) predominate in the myositis group, and 1 (anti-TIF1) in the non-myositis group (Fisher’s test). As quantitative values were found different for 5 aAbs (Mann Whitney test), a clinical threshold was calculated to discriminate myositis from non-myositis groups (ROC curve) allowing to determine an odds ratio (OR). Accordingly, 4/15 (%) aAbs were found associated with myositis: anti-SRP (at 28UA: OR=3.24 95% CI [1.01-10.46], p=0.048), anti-MDA5 (at 15UA: OR=4.36; 95% CI [1.19-15.99], p=0.048), anti-Mi2 (at 5UA: OR =3.24; 95% CI [1.01-10.46], p=0.026), anti-Jo1 (at 5UA: OR= 12.20; 95% CI [2.78-53.52], p<0.0001). All positive predictive values were improved by using a clinical threshold although some of did not reach significance due to their infrequency.ConclusionIn this retrospective work, despite missing data, the clinical phenotypes of myositis patients and their distribution according to aAbs were comparable to those in the literature. Our study confirms the lack of specificity of D-tek immunodots for IIM-specific aAbs and allows establishing new thresholds improving their performance. Our results should encourage medical biologists to establish local rules of interpretation and reinforce the interest of the discussion between Clinicians and Biologists around the interpretation of these immunodots.Figure 1.A: Odd Ratio (OR) evaluated with the manufacturer threshold ≥ 5 and B: OR using Youden’s index (clinical threshold).Disclosure of InterestsNone declared

BackgroundThe prevalence of cardiac involvement in systemic sclerosis (SSc) varies in the literature between 3% and 44% and represents a leading cause of mortality in this disease. The incidence of severe cardiac involvement and the factors associated with the occurrence of severe cardiac involvement are not known in the literature.ObjectivesThe objective of this study was to evaluate the incidence, prognosis and factors associated with the occurrence of severe cardiac involvement during SSc course.MethodsWe conducted a retrospective, bi-centric study from January 1, 1966 to December 31, 2018. The patients included had a diagnosis of SS according to the ACR/EULAR 2013 criteria. The primary endpoint was the occurrence of severe cardiac involvement. Cardiac involvement was defined by the presence of at least one of the following elements: death of cardiovascular origin, left ventricular ejection fraction less than or equal to 50%, abnormality of at least 3 measurement parameters of diastolic function, global longitudinal strain less than or equal to 18 in absolute value, ventricular tachycardia, ventricular extrasystoles requiring intervention or elevated troponin. Patients with associated myositis and whose only criterion for cardiac involvement was elevated troponin were not included in the group with cardiac involvement. Severe cardiac involvement was defined by the occurrence of hospitalization for cardiovascular reasons or by death of cardiovascular origin. Univariable and multivariable Cox proportional hazards models were used to determine variables associated with severe cardiac involvement occurrence. Survival analysis was performed using the Kaplan-Meier method with comparisons performed using the log rank test.ResultsFour hundred and fifty-nine patients with SSc were included and were followed for a median of 7.1 years [3.1; 13.3]. The median age of our population was 54 years old. There were 81% of women, 77% of patients had limited cutaneous SSc, 15% diffuse cutaneous SSc and 8% SSc sine scleroderma. Of the 459 patients, 105 (23%) had cardiac involvement and 56 (12%) severe cardiac involvement. The incidence of severe cardiac involvement was 2.42 per 100 patient years. Ninety-six hospitalizations were recorded, including 40 (42%) for acute heart failure, 19 (20%) for arrhythmia, 5 (5%) for acute pericarditis, 6 (6%) for acute myocarditis and 14 (15 %) for coronary artery disease (acute coronary syndrome, myocardial infarction or coronary revascularization). The independent factors associated with severe cardiac involvement in SSc were age over 54 years at SSc-diagnosis (OR = 3.21 95% CI [1.73; 5.95], p < 0.001), the presence of myositis (OR = 5.01 95% CI [1.89; 13.28], p = 0.001), pericardial involvement (OR = 3.79 95% CI [2.05; 7.03]; p < 0.001) or scleroderma renal crisis (OR = 4.72 95% CI [2.05; 10.92], p < 0.001). The survival rate of patients with severe cardiac involvement was 70% at 5 years and 53% at 10 years. Patients with severe cardiac involvement had a mortality risk three times greater than patients without severe cardiac involvement, HR = 3.1 (95% CI [1.7; 5.7], p<0.0001) (Figure 1). Pericardial involvement was an independent risk factor for mortality, HR = 2.0 (95% CI [1.02; 4.0], p=0.04).Figure 1.Survival of patients with severe cardiac involvement of systemic scleroderma. HR: Hazard ratio; 95% CI: 95% Confidence interval; Nb at risk: Number at riskConclusionWe need to focus our clinical attention on diagnosing and manage cardiac involvement in SSc, as severe cardiac involvement is not uncommon and is responsible for a poor prognosis.Disclosure of InterestsNone declared