Introduction Stroke is an uncommon but pivotal prognostic factor in giant cell arteritis (GCA) and Takayasu arteritis (TAK). While both conditions are large vessel vasculitis stroke characteristics may differ between them, with potential implications for diagnosis and acute management. This study aimed to compare the epidemiological, clinical, and prognostic features of stroke in GCA and TAK. Methods We conducted a multicenter retrospective cohort study including patients who met the ACR/EULAR 2022 classification criteria for GCA or TAK and experienced at least one imaging-confirmed stroke. Patients with transient ischemic attacks, strokes occurring after the age of fifty in TAK, or strokes secondary to atrial fibrillation were excluded. Results A total of 108 patients were analyzed (68 GCA, 40 TAK). The female-to-male ratio was 0.78 in GCA and 5.2 in TAK (p<0.001). Stroke occurred at a mean age of 75±12 years in GCA and 35±11 years in TAK (p<0.001). Hypertension (64.7% vs. 32.4%, p=0.003) and dyslipidemia (36.8% vs. 8.8%, p=0.002) were more frequent in GCA. Cerebellar syndrome (29.4% vs. 0%, p=0.001), cranial nerve involvement (19.7% vs. 0%, p=0.017), and sensory deficits (55.9% vs. 18.4%, p<0.001) were more frequent in GCA. Stroke involved the vertebrobasilar territory in 75% of GCA vs. 20.5% of TAK (p<0.001) and the carotid territory in 35.3% of GCA vs. 79.5% of TAK (p<0.001). Vascular intervention was required in 41% of TAK vs. 6% of GCA (p<0.001). Conclusion Stroke presentation differs between GCA and TAK, with predominant vertebrobasilar involvement in GCA. Carotid involvement is more frequent in TAK and often requires vascular procedures. These differences are crucial for appropriate management.

BACKGROUND:Takayasu arteritis is a large-vessel vasculitis with polymorphic clinical presentation and outcomes. In this large multi-ethnic Takayasu cohort, we aimed to determine how factors present at diagnosis cluster together and impact prognosis. METHODS:International multicentre retrospective cohort of consecutive patients with Takayasu arteritis fulfilling international criteria at tertiary referral centres. Clinical features, laboratory and radiological data at diagnosis were collected, as well as outcomes. A step-wise unsupervised approach was used for exploratory analyses, including principal component analysis (PCA) and hierarchical clustering on principal components. Survival curves were calculated using the Kaplan-Meier estimator. RESULTS:852 patients were included (81.5% women; median age 30.6 years). After imputation of missing data, three clusters were unraveled with a progressively lower age at diagnosis from cluster 1 to 3, named 'supra-aortic', 'abdominal' and 'diffuse', respectively. 'Supra-aortic' cluster mainly presented with supra-aortic trunks' involvement (96.6%) and significantly higher rates of cerebrovascular events (16.7%). 'Abdominal' cluster presented a marked involvement of abdominal aorta (72.1%) and renal arteries (64.6%). 'Diffuse' cluster had widespread arterial involvement and significantly more extra-vascular symptoms. Elevated acute phase reactants were seen in 49.8%, 65.8% and 98.0% of patients within 'supra-aortic', 'abdominal' and 'diffuse' clusters, respectively. Compared to the 'supra-aortic' cluster, 'abdominal' patients had the highest risk of vascular complications (HR = 1.79, 95%CI 1.12-2.87), and 'diffuse' ones the greatest risk of future relapses (HR = 2.31, 95%CI 1.81-2.95). CONCLUSION:The heterogeneous demographic, clinical, laboratory and radiological features at diagnosis split patients with Takayasu arteritis into three clusters, with prognostic implications over time.

ObjectivesBehçet’s disease (BD) is a systemic vasculitis with inflammatory lesions mediated by cytotoxic T cells and neutrophils. Here, we explore the critical involvement of NF-κB signaling pathway in proinflammatory CD8+ T cells differentiation and disease progress of BD patients.MethodsWe performed microarray gene expression analyses, flow cytometry, immunophenotyping, immunohistochemistry and functional assessments of CD8+ T cells from BD patients and HD.ResultsTranscriptionally, among the 6,595 up-regulated genes in CD8+ T cells of BD vs HD, we highlighted a great enrichment for pathways linked to NF-κB and TLR signaling (i.e. NFKB1, RELB, REL, TLR1, IRF4). Phenotypically, CD8+ T cells from BD had a higher expression of phosphorylated NF-κB (pNF-κB, 4.4 ± 0.9 vs. 1.8 ± 0.2 in MFI, p = 0.001), were more activated (higher CD11c, CD11b, CD25 and TNF-α, IFN-γ expression) and exhibited more expression of Perforin and Granzyme B (33% ± 9 vs. 9 ± 5, p = 0.009, 47% ± 8 vs.21% ± 6, p = 0.02, respectively) as compared to HD. Phosphodiesterase-4 (PDE4), an immune cell enzyme that activate the NF-κB pathway was up-regulated in blood and skin lesions of BD. In vitro and in vivo inhibition of PDE4 strongly inhibited CD8+ T cell activation, cytokine secretion, cytotoxicity and proliferation.ConclusionWe highlighted that activated CD8+ T cells through NF-κB signaling pathway are instrumental in BD.

OBJECTIVE:Patients with primary Sjögren disease (pSD) are prone to develop non-Hodgkin lymphoma (NHL), but relevant biomarkers are lacking. We aimed to determine new biomarkers predictive of NHL in patients with pSD. METHODS:Two hundred six patients with pSD fulfilling American College of Rheumatology/EULAR 2016 criteria were included and divided into three groups: pSD, lymphoproliferative pSD (Arl-pSD), and NHL-pSD. Deep flow cytometry immunophenotyping of B and T cell compartments as well as serum interferon-α (IFNα) quantification were coupled to clinical, biologic, and histopathologic data analysis. RESULTS:We identified CD11c+ FcRL5+ tissue-like memory B cells and IFNγ+ TNFα+ conventional T cells as significantly associated with NHL in pSD. These clusters showed progressive enrichment in Arl-pSD and NHL-pSD as compared to pSD. The combination of these two population abundances discriminates patients with NHL-pSD with a sensitivity of 78.9% and a specificity of 76.8%, thus overcoming alone the performance of the sum of conventional clinical and biologic markers such as cryoglobulinemia vasculitis, parotid enlargement, adapted clinical EULAR Sjögren's Syndrome Disease Activity Index, rheumatoid factor antibodies, low C4 and elevated serum IFNα levels (68.4% and 78.0%, respectively). CD11c+ FcRL5+ tissue-like memory B cells were associated with occurrence of mucosa-associated lymphoid tissue (MALT) marginal-zone NHL, whereas IFNγ+ TNFα+ conventional T cells were more indicative of non-MALT B cell NHL. CONCLUSION:We unveil novel biomarkers of NHL in pSD based on an integrative analysis coupling deep immunophenotyping and clinical, biologic, and histopathologic data. Furthermore, these markers allow distinguishing B cell NHL subtypes in pSD.

Auto-immune and inflammatory diseases are heterogenous in their clinical manifestations and prognosis, even among individuals presenting with the same pathology. Understanding the immunological alterations involved in their pathogenesis provides valuable insights in different clinical phenotypes and treatment responses. Immunophenotyping could lead to significant improvements in diagnosis, monitoring, initial treatment decisions and follow-up in autoimmune and inflammatory diseases. Mass cytometry provides measurement of over 40 simultaneous cellular parameters at single-cell resolution, and therefore holds immense potential to evaluate complex cellular systems and for high-dimensional single-cell analysis. The high dimensionality of mass cytometry provides better coverage of immune populations dynamics, with sufficient power to identify rare cell types compared to flow cytometry. In this comprehensive review, we explore how mass cytometry findings contributed in the past decade to a deeper understanding of the cellular actors involved in systemic auto-immune and auto-inflammatory diseases with their respective therapeutic and prognostic impact. We also delve into the bioinformatical approaches applied to mass cytometry to analyze the high volumes of data generated, as well as the impact of the use of complementary single cell RNA sequencing, and their spatial modalities. Our analysis highlights the fact that mass cytometry captures major information on cell populations providing insights on the complex pathogenesis of autoimmune diseases. Future research designs could include mass cytometry findings in association to other -omics to stratify patients in adequate therapeutic arms and provide advancements in personalized therapies in the field of auto-immune and inflammatory diseases.

Background Cardiac sarcoidosis (CS) is an underdiagnosed condition potentially leading to high comorbidity. Hemodynamic forces (HDFs) measure the global force exchanged between blood volume and myocardium in cardiac magnetic resonance imaging (CMR), and are a novel noninvasive parameter to detect cardiac dysfunction. HDFs have not yet been studied in patients with suspected CS. Objectives To investigate left ventricle (LV) HDFs in suspected CS compared to healthy controls (HC) and to evaluate the diagnostic role of HDFs in differentiating between confirmed CS and non-CS patients within the suspected CS group. Methods In a single-center study, patients with suspected CS and biopsy-proven sarcoidosis were included and matched to healthy controls (HCs) (Fig. 1). HDFs were measured using an advanced post-processing software. In sarcoidosis patients, cardiac involvement was confirmed using World Association for Sarcoidosis and Other Granulomatous diseases 2014 criteria. HDFs diagnostic performance for CS was studied using a logistic regression. Results Among 45 sarcoidosis patients with suspected CS, 60% had confirmed-CS (22% positive cardiac FDG-PET, 11% scintigraphy perfusion defects, 85% LGE). HDFs were significantly altered compared to HC (LV impulse, P=0.045; LV systolic ratio, P=0.018; LV systolic-diastolic transition, P=0.012; LV diastolic deceleration, P=0.013). In sarcoidosis patients, LV strain and LVEF (median [IQR]%) were not significantly different between CS (56 [53–60]) and non-CS (60 [55–64]). LV longitudinal force (P=0.041), LV impulse (P=0.018), and LV systolic peak (P=0.035) were significantly altered in confirmed-CS. The combination of LV longitudinal force, impulse, and systolic peak enabled diagnosis of CS among sarcoidosis patients with an AUC of 0.88 (Fig. 2). Conclusion Sarcoidosis patients with suspected CS had altered HDFs compared to HC due to altered LV geometry and mechanics. HDFs were superior to traditional volumetric and functional CMR parameters to predict cardiac involvement in sarcoidosis patients (Fig. 3).

Erdheim-Chester disease (ECD) is a rare histiocytic disorder with localized presentations or multisystem disease. Clinical presentations of ECD are usually non-specific and depends on the site of involvement. ECD can involve one or several organs. Clinical manifestations range from asymptomatic lesions to severe and life-threatening organ dysfunction. Hence, accurate and timely diagnosis is challenging given the rarity and varied presentation of ECD. The most common clinical manifestations are bone pain related to osteosclerosis, usually in the lower limbs. We report here a case with no obvious clinical manifestation of ECD preceding initial recurrent pleural effusions. The diagnosis of ECD was suggested based on pleural thickening revealed by relapsing pleural effusions combined with radiological finding of a coated aorta and slight perirenal infiltrate. Pleural biopsy revealed collagen fibrosis, and immunohistochemistry with the anti-CD163 antibody showed an important infiltration by histiocytes, strong cytoplasmic phosphorylated ERK in the lesional cells, and positive factor XIIIa staining. A cell-free DNA from peripheral blood revealed negative BRAF mutation and the presence of MAP2K1 mutation, a key driver mutation in ECD. The diagnosis is often suggested based on clinic-radiological presentation but requiring histopathology to establish a final diagnosis of ECD. Plasma cell-free DNA is a promising and non-invasive tool to detect key driver mutations.

Introduction La sclérodermie systémique (ScS) est une maladie du tissu conjonctif caractérisée par une inflammation, des altérations microvasculaires et une fibrose. Les comorbidités cardiaques représentent la principale cause de mortalité. Le diagnostic précoce des dysfonctionnements cardiovasculaires reste difficile avant l’apparition de manifestations cliniques. L’IRM cardiaque (IRMc) s’est imposée comme un excellent outil non invasif pour évaluer l’impact cardiologique de la ScS. Les forces hémodynamiques (HDF) sont un paramètre IRM nouvellement décrit permettant la mesure de la force globale échangée entre le volume sanguin et le myocarde, évaluée grâce à l’IRMc, en se basant sur l’équation de mécanique de fluides de Navier-Stokes. Les HDF sont particulièrement sensibles pour la détection de dysfonctionnement méchanistiques au niveau cardiaque. Dans cette étude, nous avons étudié la valeur diagnostique de la mesure des HDF chez les patients atteints de ScS comparée à celle des témoins sains, comme indicateur potentiel précoce de dysfonction cardiaque infraclinique. Patients et méthodes Dans une étude monocentrique, les patients atteints de ScS répondant aux critères de classification de l’American College of Rheumatology et de la Ligue européenne contre le rhumatisme ont été inclus et ont eu une IRM cardiaque 1,5T. Les HDF ont été mesurées à l’aide d’un logiciel de post-traitement avancé (Medis Suite, Leiden, Pays-Bas). Les mouvements issus des images de déformation des plans ciné à 2, 3 et 4 cavités ont été utilisés pour le calcul des HDF longitudinales (apical-basal) et transversales (septal-latéral) du ventricule gauche (VG). Afin de comparer différentes tailles de VG, les HDF ont été normalisées et exprimées en pourcentage de l’accélération gravitationnelle. Résultats Parmi les 11 patients atteints de ScS recrutés (âge moyen 46,27±15,2 ans, 19 % hommes), 5 (46 %) présentaient une forme diffuse et 5 (46 %) souffraient d’hypertension pulmonaire. Deux patients (18 %) avaient une dysfonction systolique du VG avec une fraction d’éjection moyenne du VG (FEVG) de 59 %. Cinq patients (46 %) présentaient une dysfonction systolique du ventricule droit (VD) avec une fraction d’éjection moyenne du VD (FEVD) de 50 %. Nous avons comparé les HDF des 11 patients ScS à celles de 11 témoins sains appariés en âge provenant d’une cohorte externe. Les patients atteints de ScS ont présenté des HDF longitudinales du VG plus importantes en systole (pour les valeurs des racines des moyennes des carrés [RMS] p=0,029, ainsi qu’aux pics de mesure, p=0,047). Ces changements peuvent être expliqués par une déformation anatomique du coeur secondaire à l’augmentation de la pression dans le VD. La décélération diastolique était significativement plus faible chez les patients ScS (p=0,040), un résultat qui pourrait indiquer une diminution de la compliance du VG dans le contexte de pressions de remplissage élevées. De plus, le ratio transverse/longitudinal et l’angle, deux paramètres HDF élevés en tant que mécanismes compensatoires, étaient fortement corrélés avec le score de Rodnan, un indicateur reconnu de la gravité de la ScS et de son pronostic. Conclusion L’analyse des HDF a le potentiel d’être utilisée comme marqueur sensible de dysfonction cardiaque chez les patients atteints de ScS par rapport aux paramètres volumétriques et fonctionnels traditionnels.

Introduction L’apparition d’une vascularite au cours de la maladie de Sjögren (SjD) est un signe d’activité dans le score Eular Sjögren Syndrome Disease Activity index (ESSDAI) et est associée au mauvais pronostic notamment en raison du risque accru de développer une hémopathie lymphoïde B. Elle est rapportée chez 9 à 15 % des patients, l’atteinte cutanée étant la plus fréquente (80 à 90 % des cas). Cependant, plusieurs types de vascularites cutanées (VC) ont été décrits au cours de la SjD, notamment les vascularites cryoglobulinémiques, hypergammaglobulinémiques et urticariennes. L’objectif était d’évaluer les caractéristiques cliniques, immunologiques et le pronostic des différents types de VC au cours de la SjD. Matériel et méthodes Étude rétrospective multicentrique incluant des patients atteints de SjD avec VC identifiés par (1) le codage des services d’anatomopathologie de 3 hôpitaux universitaires, (2) par appel à cas national. Le diagnostic de SjD était défini selon les critères ACR/EULAR. Le diagnostic de VC était défini comme certain (prouvée par biopsie) ou fortement suspecté sur la base des caractéristiques cliniques et biologiques compatibles et après évaluation faite par un dermatologue. Les étiologies de VC étaient classées selon l’addendum dermatologique de la classification de Chapel-Hill. L’activité de la SjD était évaluée par le score ESSDAI. Résultats Au total, 54 patients ont été inclus ; 49 (90,7 %) étaient des femmes. Les manifestations cutanées des vascularites comprenaient un purpura vasculaire n=50 (92,6 %), une éruption maculopapuleuse érythémateuse n=15 (27,8 %), des lésions nécrotiques/ulcérées n=15 (27,8 %), une éruption urticarienne (n=4 ; 7,4 %). Dix-huit (33,3 %) patients avaient une atteinte extra-cutanée de la vascularite : neurologique périphérique (n=15 ; 27,8 %), neurologique centrale et musculaire (n=1 respectivement). La VC était principalement classée en vascularite cryoglobulinémique (n=29 ; 56,9 %) dont 24 de type II et en vascularite hypergammaglobulinémique (n=15 ; 27,8 %). Comparés à des contrôles SjD sans VC, appariés sur la durée de suivi, issus d’une cohorte multicentrique prospective, les patients avec VC avaient une tendance à une fréquence plus élevée de lymphomes B (11,8 % vs 3,5 % ; p=0,08). Comparés aux autres types de VC, les patients avec vascularite cryoglobulinémiques de type II avaient un score ESSDAI plus élevé au moment de la VC (médiane : 15 ; IQR : 12–23 ; p=0,005), une atteinte rénale (29,2 % vs 4 % ; p=0,02) et neurologique périphérique (62,5 % vs 12 % ; p=0,0003) plus fréquentes. En utilisant le modèle de Cox, il existait un risque significativement plus élevé de décès ou de lymphome B dans les années suivant le diagnostic de VC chez les patients atteints de vascularite cryoglobulinémique de type II par rapport aux autres types de VC [hazard ratio : 6,8 (intervalle de confiance à 95 % ; 1,8–25,5) ; p=0,0046]. Discussion Nous rapportons une cohorte originale de patients atteints de SjD compliqué de VC et mettons en évidence le pronostic défavorable des cryoglobulinémies de type II comparé aux autres formes de VC. Parmi les limites on trouve le caractère rétrospectif de l’étude et l’absence de biopsie chez 48 % des patients. Conclusion Parmi les VC compliquant la maladie de Sjögren, seule la vascularite cryoglobulinémique de type II semble être associée à un pronostic péjoratif.