Anticorps anti-NuMA : associations cliniques et impact sur le phénotype de patients atteints de de syndrome de Sjögren primitif et de lupus systémique

Les anticorps (Ac) anti-NuMA représentent des auto-Ac identifiés sur une fluorescence particulière sur les cellules en mitose lors de la recherche d’Ac antinucléaires.Sur une cohorte rétrospective de 90 patients porteurs d’Ac anti-NuMA, nous avons identifié que la prévalence de ces Ac était de 0,36%. Soixante-six (73,3%) d’entre eux avaient une fluorescence anti-NuMA1 et 24 patients (26,7%) avaient une fluorescence anti-NuMA2. Parmi ces 90 patients, 70 (77,7%) souffraient d’une maladie systémique et 61 (67,8%) avaient une maladie auto-immune : syndrome de Sjögren primitif (SSp) (28,9%), lupus érythémateux systémique (LES) (21,1%), connectivite indifférenciée (7,8%), polyarthrite rhumatoïde (5,6%). Quatre patients (4,4%) présentaient une pathologie cancéreuse et quatre patients (4,4%) avaient une maladie infectieuse. Douze patients (13,3%) souffraient de maladies diverses. En réalisant une revue exhaustive de la littérature, nous avons identifié 12 études rapportant les caractéristiques de patients porteurs d’Ac anti-NuMA, qui présentaient en moyenne les mêmes caractéristiques que les patients de notre cohorte. Lorsque l’on comparait les caractéristiques entre les patients porteurs d’Ac anti-NuMA1 par rapport à ceux porteurs d’Ac anti-NuMA2, on notait un titre d’Ac antinucléaires plus élevé (1/789,7 versus 1/457,5), une association plus fréquente à d’autres auto-Ac (26,2% versus 15,9%) et une association plus fréquente aux maladies auto-immunes (72,4%, versus 60,2%) chez les patients avec Ac anti-NuMA1. Leur comparaison a permis de montrer que les patients avec des maladies auto-immunes et des anti-NuMA étaient plus jeunes (52,1 ans versus 54,7 ans), davantage des femmes (85,3% versus 66,3%) et avaient un titre d’Ac antinucléaires plus important (1/1192,3 versus 1/595,5), une association à d’autres auto-Ac (29,4% versus 8,9%) et une fluorescence anti-NuMA1 plus fréquentes (81,5% versus 66,7%) que les patients sans maladie auto-immune. Le SSp et le LES étant les deux maladies auto-immunes les plus fréquemment retrouvées chez les patients porteurs d’Ac anti-NuMA, nous avons décidé d’étudier l’impact de la présence d’Ac anti-NuMA sur le phénotype de ces patients par rapport à ceux qui ne possèdent pas de tels Ac.Nous avons comparé 20 patients atteints de SSp et porteurs d’Ac anti-NuMA à 137 patients avec SSp et sans anti-NuMA. Nous avons observé que les patients avec Ac anti-NuMA étaient moins sujets au syndrome sec ophtalmique (70% versus 89,1%, p = 0,031) ou à des complications du syndrome sec (15% versus 39,4%, p = 0,045), moins porteurs d’Ac anti-ENA (40% versus 68,6%, p = 0,022), notamment d’Ac anti-SSa et/ou SSb (40% versus 66,4%, p = 0,027), et avaient reçu moins de traitements (nombre médian de lignes de traitement : 1 versus 2, p < 0,01), et notamment d’HCQ (45% versus 70,8%, p = 0,038). Par ailleurs, il y avait une tendance, non significative, à ce que les patients avec anti-NuMA aient plus de manifestations hématologiques (30% versus 24,8%), neurologiques du SSp (15% versus 5,8%), et moins de syndrome sec buccal (80% versus 86,1%), de manifestations rhumatologiques (50% versus 60,6%) que les patients sans Ac anti-NuMA. Nous avons alors comparé 14 patients avec un LES et des Ac anti-NuMA et 80 patients atteints de LES sans anti-NuMA. Nous avons pu noter que les patients avec anti-NuMA ne présentaient pas de glomérulonéphrite lupique (0% versus 28,8%, p = 0,019) et avaient moins d’auto-Ac (50,0% versus 85,0%, p < 0,01) en particulier moins d’Ac anti-ADN natifs (42,9% versus 75,0%, p = 0,025) et d’anti-SSa/SSb (7,1% versus 45,0%, p < 0,01), moins de consommation du complément (21,4% versus 53,8%, p = 0,040), moins d’hypergammaglobulinémie polyclonale (20,0% versus 61,0%, p = 0,019) et plus de thrombopénie (35,7% versus 12,5%, p = 0,044) que les patients sans Ac anti-NuMA. Les patients avec anti-NuMA avaient reçu moins de traitement par antipaludéen de synthèse (57,1% versus 96,3%, p < 0,001), par corticoïdes (64,3% versus 92,5%, p < 0,01) et globalement moins de traitements en tout sur le suivi (nombre médian : 1,5 versus 3, p < 0,01) que les patients non porteurs d’Ac anti-NuMA. De façon non significative, les patients porteurs d’Ac anti-NuMA avaient une tendance à présenter un phénotype avec des manifestations plutôt neurologiques (14,3% versus 5%), hématologiques (78,6% versus 65%), pulmonaires (14,3% versus 6,3%) que les patients sans anti-NuMA, qui avaient un profil plus classique de LES avec manifestations cutanées (57,1% versus 78,8%) et articulaires (78,6% versus 88,8%) prédominantes.Ainsi, on a pu mettre en évidence que les patients présentant un Ac anti-NuMA avaient un profil phénotypique et évolutif particulier qui pourrait être lié au rôle particulier de ces auto-Ac dans l’activité de la pathologie auto-immune sous-jacente

Categorization of patients with systemic lupus erythematosus using disease activity, patient-reported outcomes, and transcriptomic signatures

International audienceObjective Patients with systemic lupus erythematosus (SLE) display symptoms that are not always related to disease activity and may distort clinical trial results. Recently, a clinical categorization based on the presence of type 1 (inflammatory manifestations) and/or type 2 (widespread pain, fatigue, depression) symptoms has been proposed in SLE. Our aim was to develop a type 2 score derived from the Short-Form health survey (SF-36) to categorize SLE patients and to compare immunological and transcriptomic profiles between groups.Method Seventeen items from the SF-36 were selected to build a type 2 score for 50 SLE patients (100 visits; LUPUCE cohort), and the SLEDAI was used to define type 1 symptoms. Patients were categorized into four groups: minimal (no symptoms), type 1, type 2, and mixed (both type 1 and type 2 symptoms). Clinical, immunological, and transcriptomic profiles were compared between the groups.Results Type 2 scores ranged from 0 to 31, with a cutoff value of 14 (75th percentile). The sample categorization was minimal in 39%, type 1 in 37%, and type 2 in 9%, and mixed in 15%. Type 2 patients were older than minimal patients and had a longer disease duration than type 1 and mixed patients. Immunological data and modular interferon signatures did not differ between the groups.Conclusion Patients with SLE can be categorized into four clinical groups using the SLEDAI score and our SF-36-derived type 2 score. This categorization is non-redundant with immunological or transcriptomic profiles and could prove useful to stratify patients in clinical trials

Characteristics of JAK2 unmutated erythrocytosis: Distinctive traits between polycythemia vera and non-polycythemia vera patients

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Views of Medical Examiners and Psychiatrists on the Compatibility of the Mental State with Detention in Police Custody in Marseille University Hospital

International audiencePolice custody is detention in response to a suspicion of crime. A person in custody has the right to be examined by a physician, who is responsible for determining whether the person's medical condition allows him/her to continue to be held in detention. However, there is no consensus on the definition of compatibility of the mental state with custody. Our objective was to determine the relevant criteria for compatibility and incompatibility of the mental state with detention in police custody according to medical examiners and psychiatrists. A descriptive study using a semi-structured questionnaire was conducted from November 2016 to May 2017 with medical examiners and psychiatrists who examined detainees in police custody in Marseille. We recruited 17 medical examiners and 43 psychiatrists. We identified three sets of criteria used to determine a mental state compatible with custody: care, pathology/disorder, and the context of police custody. The primary determinant of incompatibility was a need for immediate hospitalization, followed by a high suicide risk, psychiatric dangerousness, delusional symptomatology, an inability to understand questions, and an inability for the detainee to defend him-/herself. The psychiatrists and medical examiners differed significantly in their views of suicide risk, delusional symptomatology, and psychiatric diagnosis. Our work has permitted identification of the main determinants of incompatibility of the mental state with custody according to psychiatrists and medical examiners in Marseille. It offers preliminary results to reach a consensus and provide an inventory for physicians to use regarding police custody

Axial articular manifestations in primary Sjögren‘s syndrome: Association with spondyloarthritis

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Combining systemic and locally applied cellular therapies for the treatment of systemic sclerosis

International audienceSystemic sclerosis (SSc) is a complex autoimmune disease characterized by a functional and structural alteration of the microvascular network associated with cutaneous and visceral fibrosis lesions. Conventional therapies are based on the use of immunomodulatory molecules and symptomatic management but often prove to be insufficient, particularly for patients suffering from severe and rapidly progressive forms of the disease. In this context, cellular therapy approaches could represent a credible solution with the goal to act on the different components of the disease: the immune system, the vascular system and the extracellular matrix. The purpose of this review is to provide an overview of the cellular therapies available for the management of SSc. The first part will focus on systemically injected therapies, whose primary effect is based on immunomodulatory properties and immune system resetting, including autologous hematopoietic stem cell transplantation and intravenous injection of mesenchymal stem cells. The second part will discuss locally administered regenerative cell therapies, mainly derived from adipose tissue, developed for the management of local complications as hand and face disabilities

Cytological Diagnosis of Classic Myeloproliferative Neoplasms at the Age of Molecular Biology

Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell-derived disorders characterized by uncontrolled proliferation of differentiated myeloid cells. Two main groups of MPN, BCR::ABL1-positive (Chronic Myeloid Leukemia) and BCR::ABL1-negative (Polycythemia Vera, Essential Thrombocytosis, Primary Myelofibrosis) are distinguished. For many years, cytomorphologic and histologic features were the only proof of MPN and attempted to distinguish the different entities of the subgroup BCR::ABL1-negative MPN. World Health Organization (WHO) classification of myeloid neoplasms evolves over the years and increasingly considers molecular abnormalities to prove the clonal hematopoiesis. In addition to morphological clues, the detection of JAK2, MPL and CALR mutations are considered driver events belonging to the major diagnostic criteria of BCR::ABL1-negative MPN. This highlights the preponderant place of molecular features in the MPN diagnosis. Moreover, the advent of next-generation sequencing (NGS) allowed the identification of additional somatic mutations involved in clonal hematopoiesis and playing a role in the prognosis of MPN. Nowadays, careful cytomorphology and molecular biology are inseparable and complementary to provide a specific diagnosis and to permit the best follow-up of these diseases

Persistent IgG anticardiolipin autoantibodies are associated with post-COVID syndrome

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