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Little is known about the prevalence and factors associated with long-term remission in cutaneous lupus erythematosus (CLE).To assess the prevalence, the factors associated with remission, and the long-term remission with and without treatment during CLE.Longitudinal cohort study including biopsy-proven patients with CLE seen between November 1, 2019 and April 30, 2021, with at least 6 months of follow-up after diagnosis. Demographic data, CLE subtypes, remission status, and treatments were recorded. Remission was defined by a Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score of 0. Long-term remission was defined by remission3 years.Among 141 patients included (81% of women), 93 (66%) were in remission at last follow-up with a median duration since diagnosis of 11.4 years (interquartile range, 4.2-24.7). Long-term remission was observed in 22 (19%) of 114 patients with at least 3 years of follow-up, including 5 (4.4%) with no systemic treatment. Active smoking (odds ratio, 0.22 [95%CI: 0.05-0.97]; P = .04) and discoid CLE lesions (odds ratio, 0.14 [95%CI, 0.04-0.48]; P = .004) were associated with a lower risk of long-term remission.Partial retrospective data collection and tertiary center population.Long-term remission is rare in CLE and negatively associated with active smoking and discoid CLE.

Objective To help identify homogeneous subgroups among patients with anti-PM-scleroderma-antibodies (PM-Scl-Abs) positive auto-immune diseases regardless of diagnostic classifications. Material and methods This multicentric (four hospitals) retrospective study collected all consecutive patients (from 2011 to 2021) with positive testing for anti-PM-Scl-Abs in a context of CTD. Subgroups of patients with similar clinico-biological phenotypes were defined using unsupervised multiple correspondence analysis and hierarchical clustering analysis of the features recorded in the first year of follow-up. Results One hundred and forty-two patients with anti-PM-Scl-Abs were evaluated and 129 patients were included in the clustering analysis and divided into three clusters. Cluster 1 (n = 47) included patients with frequent skin thickening, digestive involvement and interstitial lung disease (ILD) with non-specific interstitial pneumonia (NSIP). They were more likely to develop progressive fibrosing ILD. Cluster 2 (n = 36) included patients who all featured NSIP with frequent organizing pneumonia–associated pattern and mechanic’s hands. This subgroup had increased risk of relapse and ILD was characterized by a good functional outcome. Cluster 3 (n = 46) was characterized by predominant or isolated musculoskeletal involvement and frequently matched UCTD criteria. Although very frequent among anti-PM-Scl-Abs positive patients, muscle involvement was less discriminating compared with skin thickening and ILD pattern to classify patients into subgroups. Conclusion Anti-PM-Scl-Abs associated auto-immune diseases are segregated into three subgroups with distinct clinical phenotype and outcomes. Skin thickening and NSIP are determinant predictors in segregation of theses populations.

Objectives To describe the clinical and pathological features of biopsy-proven cutaneous vasculitis (CV) associated with SLE, focusing on diagnosis classification and impact on overall SLE activity. Methods Retrospective multicentric cohort study including SLE patients with biopsy-proven CV identified by (i) data from pathology departments of three university hospitals and (ii) a national call for cases. SLE was defined according to 1997 revised ACR and/or 2019 ACR/EULAR criteria. CV diagnosis was confirmed histologically and classified by using the dermatological addendum of the Chapel Hill classification. SLE activity and flare severity at the time of CV diagnosis were assessed independently of vasculitis items with the SELENA-SLEDAI and SELENA-SLEDAI Flare Index. Results Overall, 39 patients were included; 35 (90%) were female. Cutaneous manifestations included mostly palpable purpura (n = 21; 54%) and urticarial lesions (n = 18; 46%); lower limbs were the most common location (n = 33; 85%). Eleven (28%) patients exhibited extracutaneous vasculitis. A higher prevalence of Sjögren’s syndrome (51%) was found compared with SLE patients without CV from the French referral centre group (12%, P Conclusion SLE-related vasculitis seems very rare and other causes of vasculitis should be ruled out before considering this diagnosis. Moreover, in more than half of patients, CV was not associated with another sign of active SLE.

ObjectivesType-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes are strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown.MethodsWe retrospectively analysed a monocentric longitudinal cohort of 609 patients with SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed by abolishment of Madin-Darby bovine kidney cell protection by IFN-α2 against vesicular stomatitis virus challenge. Serum-neutralising activity against IFN-α2, IFN-β and IFN-ω was also determined with a reporter luciferase activity assay. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns.ResultsNeutralising and non-neutralising anti-IFN-α antibodies are present at a frequency of 3.3% and 8.4%, respectively, in individuals with SLE. AAbs neutralising IFN-α, unlike non-neutralising AAbs, are associated with reduced IFN-α serum levels and a reduced likelihood to develop active disease. However, they predispose patients to an increased risk of herpes zoster and severe COVID-19 pneumonia. Severe COVID-19 pneumonia in patients with SLE is mostly associated with combined neutralisation of different IFNs-I. Finally, anti-IFN-α AAbs do not interfere with COVID-19 vaccine humoral immunogenicity.ConclusionThe production of non-neutralising and neutralising anti-IFN-I antibodies in SLE is likely to be a consequence of SLE-associated high IFN-I serum levels, with a beneficial effect on disease activity, yet a greater viral risk. This finding reinforces the recommendations for vaccination against SARS-CoV-2 in SLE.

ObjectivesOur aims were to evaluate Systemic Lupus Erythematosus (SLE) disease activity and SARS-CoV-2 specific immune responses after BNT162b2 vaccination.MethodsIn this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine, until day 15 after the second dose in 126 SLE patients. SARS-CoV-2 antibody responses were measured against wild-type spike antigen while serum-neutralizing activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T-cell responses were quantified by Interferon (IFN)-γ release assay after the second dose.ResultsBNT162b2 was well tolerated and no statistically significant variations of BILAG and SLEDAI scores were observed throughout the study in SLE patients with active and inactive disease at baseline. Mycophenolate Mofetil (MMF) and Methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody-response (β=-78; p=0.007, β=-122; pConclusionMMF, MTX and poor baseline humoral immune status, particularly: low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating SLE patients who might need adapted vaccine regimens and follow-up.KEY MESSAGESWhat is already known about this subject?BNT162b2 efficacy and safety has been described in studies mixing different RMDsWhat does this study add?No serious adverse effects, nor SLE flares have been documented after BNT162b2 in SLE patients.Not only MMF and MTX, but also a poor humoral immune status at baseline impair vaccine antibody responseAlbeit decreased, serum neutralizing activity against VOCs is conferred to vaccine-responders.How might this impact on clinical practice or future developments?These parameters could be helpful for physicians to delineate which patients should have antibody measurement after full BNT162b2 vaccination and should be proposed a third injection of BNT162b2 vaccine.

Introduction: HIV infection has been recently retained as an unclear cause of AA amyloidosis. Our aim was to investigate cases of AA amyloidosis associated with HIV infection to understand if it could be considered as a cause of AA amyloidosis. Methods: A comprehensive literature review was conducted as well as retrospective study from French cases collected from our national reference center for AA amyloidosis. Results: Altogether, 19 patients with AA amyloidosis and HIV infection were found with 68% of men and median age at amyloidosis diagnosis of 38 years (range 28–75 years). Clinical presentation was nephrotic syndrome in 94% (n = 17/18). Among patients with renal involvement and assessable outcome (n = 17), 11 (64.7%) progressed to chronic kidney disease, with 6 (35%) end-stage renal disease. Seventy-five percent of patients had uncontrolled HIV infection and 71.4% CD4 counts 3 at amyloidosis diagnosis. Repeated or chronic bacterial or fungal infection was found in 47% of cases and a history of parenteral drug use in 55% of patients. Three patients had no classical or at least no suspected AA amyloidosis cause found or reported. Conclusions: AA Amyloidosis is a rare condition in HIV patients with common renal involvement and significant risk of progression to chronic renal insufficiency. Because of the frequency related to other inflammatory conditions in this population, HIV is probably not an independent risk factor for AA amyloidosis.

Resume Introduction Les auto-anticorps aident le clinicien a classer les maladies auto-immunes systemiques en sous-groupes homogenes selon le phenotype clinique et le pronostic associe. Les anticorps anti-PM-Scl, tres rarement observes, ont ete decrits au cours de differentes connectivites. En particulier, ils ont ete associes aux myopathies inflammatoires, a la sclerodermie systemique (ScS), au lupus systemique, a la maladie de Gougerot Sjogren et aux connectivites mixtes ou non classees. Notre objectif etait de decrire le spectre clinique des maladies associees aux anti-PM-Scl, en s’affranchissant des classifications diagnostiques, afin d’identifier des sous-groupes homogenes en termes clinique et pronostic. Patients et methodes Etude multicentrique (4 hopitaux) observationnelle et retrospective incluant les patients testes positifs pour les anticorps anti-PM-Scl en immuno-blot entre 2005 et 2020 dans un contexte de maladie systemique et/ou de pneumopathie interstitielle diffuse (PID). Les donnees epidemiologiques, cliniques, biologiques et radiologiques ont ete collectees de facon standardisee de meme que l’evolution de la maladie. Resultats Cent vingt-huit patients (femmes n = 96 ; 75 %) ont ete inclus. L’âge median [inter-quartiles] au diagnostic etait de 50 ans [18-84] et la duree du suivi de 7 [3,7-12] ans. Soixante-seize patients (59,3 %) avaient uniquement un anti-PM-Scl et les autres avaient au moins un autre anticorps associe : anticorps associes aux ScS (n = 21 ; 16,4 %), anti-SSA/Ro52 (n = 13 ; 10,9 %), anti-DNA natifs (n = 9 ; 7 %), anti-RNP (n = 6 ; 4,7 %) ou anti-CCP (n = 6 ; 4,7 %). Une majorite de patients presentaient une PID (n = 83 ; 65,8 %). Le pattern scannographique etait domine par la pneumonie interstitielle non specifique (92,7 %) avec une pneumonie organisee (PO) dans 25,3 % des cas. La PID etait caracterisee par une installation subaigue ( Conclusion Conduite sur une large serie de patients ayant des anti-PM-Scl, cette etude met en evidence deux principaux groupes qui se distinguent par un phenotype clinique et des modalites evolutives differentes. L’un est associe a une atteinte musculaire et une PID subaigue avec des rechutes plus frequentes. Le second est marque par un phenotype vasculaire associe a une PID d’apparition plus insidieuse, une atteinte digestive, une evolution chronique et une incidence accrue de deces.

Interferons interfere with lung repair Interferons (IFNs) are central to antiviral immunity. Viral recognition elicits IFN production, which in turn triggers the transcription of IFN-stimulated genes (ISGs), which engage in various antiviral functions. Type I IFNs (IFN-α and IFN-β) are widely expressed and can result in immunopathology during viral infections. By contrast, type III IFN (IFN-λ) responses are primarily restricted to mucosal surfaces and are thought to confer antiviral protection without driving damaging proinflammatory responses. Accordingly, IFN-λ has been proposed as a therapeutic in coronavirus disease 2019 (COVID-19) and other such viral respiratory diseases (see the Perspective by Grajales-Reyes and Colonna). Broggi et al. report that COVID-19 patient morbidity correlates with the high expression of type I and III IFNs in the lung. Furthermore, IFN-λ secreted by dendritic cells in the lungs of mice exposed to synthetic viral RNA causes damage to the lung epithelium, which increases susceptibility to lethal bacterial superinfections. Similarly, using a mouse model of influenza infection, Major et al. found that IFN signaling (especially IFN-λ) hampers lung repair by inducing p53 and inhibiting epithelial proliferation and differentiation. Complicating this picture, Hadjadj et al. observed that peripheral blood immune cells from severe and critical COVID-19 patients have diminished type I IFN and enhanced proinflammatory interleukin-6– and tumor necrosis factor-α–fueled responses. This suggests that in contrast to local production, systemic production of IFNs may be beneficial. The results of this trio of studies suggest that the location, timing, and duration of IFN exposure are critical parameters underlying the success or failure of therapeutics for viral respiratory infections. Science , this issue p. 706 , p. 712 , p. 718 ; see also p. 626

BackgroundCoronavirus disease 2019 (Covid-19) is a major global threat that has already caused more than 100,000 deaths worldwide. It is characterized by distinct patterns of disease progression implying a diverse host immune response. However, the immunological features and molecular mechanisms involved in Covid-19 severity remain so far poorly known.MethodsWe performed an integrated immune analysis that included in-depth phenotypical profiling of immune cells, whole-blood transcriptomic and cytokine quantification on a cohort of fifty Covid19 patients with a spectrum of disease severity. All patient were tested 8 to 12 days following first symptoms and in absence of anti-inflammatory therapy.ResultsA unique phenotype in severe and critically ill patients was identified. It consists in a profoundly impaired interferon (IFN) type I response characterized by a low interferon production and activity, with consequent downregulation of interferon-stimulated genes. This was associated with a persistent blood virus load and an exacerbated inflammatory response that was partially driven by the transcriptional factor NFĸB. It was also characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling as well as increased innate immune chemokines.ConclusionWe propose that type-I IFN deficiency in the blood is a hallmark of severe Covid-19 and could identify and define a high-risk population. Our study provides a rationale for testing IFN administration combined with adapted anti-inflammatory therapy targeting IL-6 or TNF-α in most severe patients. These data also raise concern for utilization of drugs that interfere with the IFN pathway.

Introduction Les anticorps (Ac) anti-polymyosite/sclerodermie (anti-PM/Scl) ont ete rapportes comme pouvant etre associes a la sclerodermie systemique (ScS). Cette cohorte etudie le profil de patients francais avec une ScS et des Ac anti-PM/Scl en les comparant a des patients atteints de ScS sans Ac anti-PM/Scl. Patients et methodes Etude retrospective menee a l’Hopital Cochin entre 2005 et 2019 incluant tous les patients ayant des Ac anti-PM/Scl positifs associes a une ScS selon les criteres, datant de 2013, de l’American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR). Les cas ont ete apparies a des patients ayant une ScS et des Ac anti-PM/Scl negatifs (2 controles pour 1 cas). L’objectif principal de l’etude etait de decrire le phenotype et le profil evolutif des patients ayant une ScS et des Ac anti-PM/Scl positifs. Resultats Cinquante-trois patients avec Ac anti-PM/Scl positifs ont ete compares a 102 patients negatifs pour les Ac anti-PM/Scl. Quatre-vingt-quatorze patients (60,6 %) avaient une ScS de forme cutanee limitee (lScS) et 61 (39,4 %) une forme cutanee diffuse (dScS). En analyse univariee, le nombre de patients presentant une atteinte musculaire (66 % versus 39 %, p = 0,002) et une forme lScS (72 % versus 55 %, p = 0,042) etait plus importants dans le groupe avec positivite des Ac anti-PM/Scl. La presence d’un phenomene de Raynaud (88 % versus 100 %, p = 0,001) et d’Ac anti-centromeres (ACA) (6 % versus 34 %, p Conclusion Dans notre cohorte, les Ac anti-PM/Scl etaient associes aux ScS cutanee limitee et a la presence d’une atteinte musculaire mais, pas a la presence d’ACA. Les Ac anti-PM/Scl semblent constituer un phenotype a part chez les patients sclerodermiques.

Introduction L’implication du virus Epstein-Barr (EBV) est fortement suspectee dans la physiopathologie du lupus systemique (LS). L’EBV est un herpes virus ubiquitaire dont la cible cellulaire principale est le lymphocyte B. Il induit aussi la production d’interferon-alpha par les cellules dendritiques plasmacytoides. Les profils serologiques EBV et sa replication peripherique suggerent une reactivation plus frequente chez les patients lupiques que dans la population generale. Habituellement la proliferation lymphocytaire B induite par l’EBV ne se manifeste que dans des conditions immunosuppressives. L’objectif de notre etude etait d’analyser le lien entre la replication peripherique de l’EBV et l’activite du LS. Patients et methodes Etude retrospective monocentrique transversale. Etaient eligibles les patients de plus de 18 ans avec un diagnostic de LS selon les criteres ACR ou SLICC et ayant eu au moins une mesure de la replication sanguine de l’EBV par polymerase chain reaction (PCR) entre 2012 et 2019 dans le meme laboratoire de virologie. Une charge virale (CV) > 125 UI/mL etait consideree comme positive. Les criteres d’exclusion etaient : patients transplantes d’organe et patients avec une serologie EBV negative. Une maladie lupique etait definie comme active en cas de score SELENA-SLEDAI > 4. La severite des poussees etait classee selon l’index des poussees SELENA-SLEDAI. Resultats Cent cinq patients (98 femmes et 7 hommes) ont ete inclus. Lors de la mesure de la replication de l’EBV : la mediane (quartiles) de l’âge et de l’anciennete du LS etaient respectivement de 34 (23,5–43) et 7 (2–14) ans ; 67 malades (70 %) etaient traites par hydroxychloroquine (HCQ), 66 (63 %) par prednisone et 42 (40 %) par un immunosuppresseur ; le score SELENA-SLEDAI median (quartiles) etait 5 (2–11) ; 60 malades (57 %) avaient un LS actif se manifestant par une polyarthrite (n = 32 ; 53 %), des symptomes systemiques (fievre, perte de poids, anorexie ou adenopathie) chez 31 (52 %), une atteinte cutanee chez n = 23 (38 %), une glomerulonephrite chez 19 (32 %), une atteinte hematologique chez 14 (23 %), une atteinte neurologique chez 13 (24 %) et une serite chez 10 (17 %). Quarante-huit (46 %) malades n’avaient pas de poussee, 19 (31 %) une poussee legere a moderee et 38 (36 %) une poussee severe. La PCR EBV etait positive chez 54 (90 %) malades ayant un lupus actif versus 6 (13 %) malades avec lupus inactif (p La charge virale EBV etait correlee au score d’activite du lupus, le SELENA-SLEDAI (r = 0,67 ; p Dix-huit malades actifs ont eu une deuxieme mesure de PCR EBV. La mediane [extremes] des CV EBV etait significativement plus importante lors des periodes d’activite du LS (236 [0–2680] UI/mL) que lors des periodes d’inactivite ou de moindre activite du LS (0 [0–1537] UI/mL, p Conclusion La presence et la severite d’une activite clinique au cours du LS sont associees a une replication peripherique de l’EBV, sans que l’on puisse definir actuellement s’il s’agit d’une cause ou d’une consequence de l’activite du systeme immunitaire.

Background:Autoantibodies permit to classify and subgroup connective tissue diseases (CTD) in homogeneous groups of patients in terms of phenotype and prognosis. Anti PM-Scl antibodies have been associated with different CTD categories such as: idiopathic inflammatory myositis (IIM), systemic sclerosis (SSc), Sjögren’s syndrome (SjS), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD) or undifferentiated connective tissue disease (UCTD).Objectives:To determine clinical spectrum of anti-PM-Scl associated disease and if it an homogenous condition.Methods:This multicentric (four hospitals) observational and retrospective study included all consecutive patients with positive testing for anti PM-Scl antibodies on immunoblot assay and connective tissue disease (2011 -2020). Epidemiological, biological, clinical and radiological data were collected in standard form as well as patient’s outcome.Results:One hundred twenty height patients (female n=96;75%) were included. Median [quartiles] age at diagnosis was 50 [18;84] (IQR) and follow-up duration of 7 [3.75-12] years. Seventy-six (59.3%) patients were simple anti-Pm-Scl positive, and 40.7% were associated with other antibodies: anti-SSA/Ro52 (n=13; 10.92%), SSc associated antibodies (n=21; 16.4%), anti-dsDNA for (n=9; 7%), anti-RNP (n=6; 4.7%) and anti-CCP antibodies (n=6; 4.7%). Most patients had cutaneous involvement (n=106; 83%) with skin thickening (n=47; 36%), mechanics hands (n= 28; 22%), calcinosis (n=26; 20.3%) and subcutaneous edema (n=20; 15.62%). Vascular involvement was frequent with Raynaud phenomenon (n= 89; 69%), telangiectasia (n=36; 28%), skin ulcers (n=27; 21%), pulmonary hypertension (n=8/120; 6.7%) and scleroderma renal crisis (n=2; 1.5%). A majority of patients also displayed an interstitial lung disease (ILD) (n=83; 65.8%); nonspecific interstitial pneumonia (92.7%) and/or organizing pneumonia (25.3%). ILD was characterized by a subacute onset in 37/81 (45.7%); median [quartiles] forced vital capacity (FVC) and total lung capacity (TLC) at diagnosis of 88% [73-105] and 79.5% [68.5-101] respectively. Sixty patients (47%) had muscular sign including myalgia (47%), elevated CPK (n=51; 40%) and muscular weakness (Medical Research Council score Conclusion:Conducted on the largest cohort of Anti-PM-Scl patients, this study highlights two main phenotypes that determine different outcome and prognosis. One was associated with muscular disease and subacute onset ILD with more frequent relapses. The second with a vascular phenotype associated with chronic ILD, digestive involvement, chronic evolution and increased incidence of death. This could lead to a reclassification of PM-Scl associated auto immune diseases.Disclosure of Interests:None declared

Background:A role for Epstein Barr Virus (EBV) infection in Systemic Lupus Erythematosus (SLE) pathogenesis is highly suspected. The frequency of EBV seroprevalence and DNA detection in peripheral blood mononuclear cells are increased in SLE patients compared to healthy controls.Objectives:To analyse the relationship between EBV blood replication and SLE disease activity.Methods:Monocentric, observational and retrospective study of SLE patients (ACR or SLICC criteria) who have had a blood EBV DNA assessment using Polymerase Chain Reaction (artus® EBV Virus QS-RGQ assay) between 2012 and 2018. Exclusion criteria were: organ or bone marrow transplant, absence of EBV seroconversion and insufficient data. SLE clinical features, the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) flare index (SFI) and therapeutic regimen on the day of EBV DNA load assessment were recorded. A SELENA-SLEDAI score > 4 defined an active SLE. A blood EBV DNA load ≥125 IU/mL was defined as elevated.Results:A total of 105 patients (98 women and 7 men) were included in the study. At inclusion, median (quartiles) age and SLE duration were 34 (23.5-43) and 7 (2-14) years old, respectively. Treatment were hydroxychloroquine (HCQ) (n = 67; 64%), prednisone (n = 66; 63%) with an average (±Standard Deviation) dose of 11.3 (±16) mg/day and an immunosuppressant (n = 42; 40%). According to SFI, 57 SLE patients were experiencing a flare at the time of EBV assessment; flares were classified as severe and mild/moderate in 38 (36%) and 19 (18%) SLE patients, respectively. According to the SELENA-SLEDAI score, 60 patients (57%) were deemed active and 45 (43%) inactive. Main clinical manifestations were arthritis in 32 (30%) patients, constitutional symptoms (fever, weight loss, anorexia or lymphadenopathy) in 31 (30%), cutaneous involvement in 23 (22%), glomerulonephritis in 19 (18%), cytopenia in 14 (13%), neuropsychiatric involvement in 13 (12%) and serositis in 10 (16%). Blood EBV DNA was elevated in 54 (90%) of the 60 patients with active lupus versus 6 (13%) of the 45 patients with inactive SLE (p -4). It was increased in 34 (89%) of the 38 patients with severe flare, in 17 (89%) of the 19 patients with a mild/moderate flare (p = 1) and in 8 (17%) of the 48 patients without flare (p -4vs severe flare and p -4vs mild/moderate flare). EBV DNA load correlated with SELENA-SLEDAI score (r=0.58; p-4in paired analysis).Conclusion:Blood EBV viral load is dramatically increased in active phase of SLE, independently of the treatment. We were unable to demonstrate whether the replication of EBV was the cause or the consequence or just an epiphenomenon of the disease activity. Further studies are needed to study whether EBV viral load is linked with Interferons secretion or B lymphocyte activation.Disclosure of Interests:None declared