Does the impact of COVID-19 on patients with systemic sclerosis change over time?

Objective: The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. Methods: Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. Results: A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. Conclusion: The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors

Phenotypic and functional characterization of regulatory B lymphocytes in Chronic Lymphocytic Leukemia : rational with disease progression

La Leucémie Lymphoïde Chronique (LLC) se caractérise par une hétérogénéité d’évolution avec des formes indolente et progressive. Cette dernière reste incurable avec les options thérapeutiques classiques. Mon objectif de thèse a consisté à définir phénotypiquement et fonctionnellement le potentiel régulateur des lymphocytes B de LLC induisant un contexte favorable à leur survie. Après purification des cellules B leucémiques de 30 patients LLC, nos résultats montrent que les sous-populations B sécrètent des cytokines immuno-régulatrices dont l’IL-10 et le TGFβ1. De façon intéressante, ces sous-populations lymphocytaires expriment également le facteur de transcription FOXP3, caractéristique des cellules T régulatrices. La signature phénotypique de ces sous-populations est spécifique au néoplasme avec des marqueurs de lymphocytes B mémoires activés. Nos approches fonctionnelles in vitro démontrent que ces sous-populations B modulent la prolifération et orientent la différenciation et les sécrétions des cellules T, contribuant à l’absence d’immuno-surveillance chez les patients. Enfin, une analyse statistique combinant les expressions de l’IL-10, du TGFβ1 et de FOXP3 dans ces sous-populations B permet de définir un indice polyfonctionnel qui corrèle avec deux facteurs clés du risque de progression de la LLC. L’ensemble de mes travaux de thèse a permis de caractériser de nouvelles sous-populations B impliquées dans la progression de la maladie et donne un rationnel à la survie des cellules leucémiques dans l’environnement ganglionnaire.Chronic Lymphocytic Leukemia (CLL) is a clonal B cell malignancy of the elderly. This neoplasm is characterized by a heterogeneous clinical course from indolent chronic disease to progressive lymphadenopathy that remains incurable. The aim of my PhD was to undertake a comprehensive phenotypic and functional analysis of the B cell subpopulations responsible for their survival advantage. CLL B cell purification from 30 patients indicate the presence in various extents of leukemic B cell subpopulations producing immune-regulatory cytokines, notably IL-10 and TGFβ1. Remarkably, these CLL subpopulations express the FOXP3 transcription factor, a marker of regulatory T cells. These subpopulations present a phenotypic signature, distinguishable from regulatory B cells populations, with specific markers of activated memory B cells. Functional studies prove their regulatory capacities on T cell differentiation, proliferation and secretion, contributing to the T cell dysfunction observed in CLL. Finally, statistical analysis combining IL-10, TGFβ1 and FOXP3 expressions for these subpopulations allows generating a poly-functional index correlated with two major risk factors of CLL progression. Our data characterize novel CLL B cell subpopulations that are involved in disease progression and give a rational to CLL B cell survival in secondary lymphoid organs

Population B régulatrice dans la leucémie lymphoïde chronique : phénotype et interactions fonctionnelles avec les lymphocytes T en lien avec l’évolutivité

Chronic Lymphocytic Leukemia (CLL) is a clonal B cell malignancy of the elderly. This neoplasm is characterized by a heterogeneous clinical course from indolent chronic disease to progressive lymphadenopathy that remains incurable. The aim of my PhD was to undertake a comprehensive phenotypic and functional analysis of the B cell subpopulations responsible for their survival advantage. CLL B cell purification from 30 patients indicate the presence in various extents of leukemic B cell subpopulations producing immune-regulatory cytokines, notably IL-10 and TGFβ1. Remarkably, these CLL subpopulations express the FOXP3 transcription factor, a marker of regulatory T cells. These subpopulations present a phenotypic signature, distinguishable from regulatory B cells populations, with specific markers of activated memory B cells. Functional studies prove their regulatory capacities on T cell differentiation, proliferation and secretion, contributing to the T cell dysfunction observed in CLL. Finally, statistical analysis combining IL-10, TGFβ1 and FOXP3 expressions for these subpopulations allows generating a poly-functional index correlated with two major risk factors of CLL progression. Our data characterize novel CLL B cell subpopulations that are involved in disease progression and give a rational to CLL B cell survival in secondary lymphoid organs.La Leucémie Lymphoïde Chronique (LLC) se caractérise par une hétérogénéité d’évolution avec des formes indolente et progressive. Cette dernière reste incurable avec les options thérapeutiques classiques. Mon objectif de thèse a consisté à définir phénotypiquement et fonctionnellement le potentiel régulateur des lymphocytes B de LLC induisant un contexte favorable à leur survie. Après purification des cellules B leucémiques de 30 patients LLC, nos résultats montrent que les sous-populations B sécrètent des cytokines immuno-régulatrices dont l’IL-10 et le TGFβ1. De façon intéressante, ces sous-populations lymphocytaires expriment également le facteur de transcription FOXP3, caractéristique des cellules T régulatrices. La signature phénotypique de ces sous-populations est spécifique au néoplasme avec des marqueurs de lymphocytes B mémoires activés. Nos approches fonctionnelles in vitro démontrent que ces sous-populations B modulent la prolifération et orientent la différenciation et les sécrétions des cellules T, contribuant à l’absence d’immuno-surveillance chez les patients. Enfin, une analyse statistique combinant les expressions de l’IL-10, du TGFβ1 et de FOXP3 dans ces sous-populations B permet de définir un indice polyfonctionnel qui corrèle avec deux facteurs clés du risque de progression de la LLC. L’ensemble de mes travaux de thèse a permis de caractériser de nouvelles sous-populations B impliquées dans la progression de la maladie et donne un rationnel à la survie des cellules leucémiques dans l’environnement ganglionnaire

Apport de l IRM cardiaque dans l évaluation du pronostic de l amylose AL

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Response letter to “Latent class analysis of 216 patients with adult-onset Still’s disease” by Sugiyama et al.

Abstract Sugiyama et al. recently described in “Latent class analysis of 216 patients with adult-onset Still’s disease,” baseline characteristics, laboratory tests, treatment, relapse, and death of adult-onset Still’s disease (AOSD) patients from a Japanese hospital. They identified two subgroups: Class 1 (n=155) with a younger age and typical symptoms of AOSD and Class 2 (n=61) with older patients and fewer typical symptoms of AOSD. In 2022, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, an established X-linked disease associated with a somatic mutation in UBA1, is considered as a differential diagnosis for AOSD particularly in elderly. These patients from Class 2 could benefit from more explorations for mild myelodysplasia and VEXAS

Inefficacy of plasma exchanges associated to rituximab in refractory obstetrical antiphospholipid syndrome

none6sinoneAbisror, Noémie; Mekinian, Arsène; Brechignac, Sabine; Ruffatti, Amelia; Carbillon, Lionel; Fain, OlivierAbisror, Noémie; Mekinian, Arsène; Brechignac, Sabine; Ruffatti, Amelia; Carbillon, Lionel; Fain, Olivie

Adult’s onset Still disease occurring during pregnancy: Case-report and literature review

International audienceAdult onset Still’s disease is a rare affection classified among non-hereditary autoinflammatory diseases. The clinical presentation goes from fever with arthralgia and maculopapular eruption to life-threatening manifestations such as secondary lymphohistiocytosis. The mechanisms of AOSD remains unclear, but seems implicate NK cells dysfunction with pro-inflammatory cytokines secretion including IL-1ß, IL-6 and IL-18 [1]. Several reports mentioned AOSD occurring during pregnancy, mostly in first and second trimester and there is still a debate on whether it could compromise or not the pregnancy outcome. We here report a case of AOSD revealed during pregnancy with a life-threatening presentation along with a review of 19 cases from literature

PET/MRI in large-vessel vasculitis: clinical value for diagnosis and assessment of disease activity

International audienceDiagnosis of large vessel vasculitis (LVV) and evaluation of its inflammatory activity can be challenging. Our aim was to investigate the value of hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) in LVV. All consecutive patients with LVV from the Department of Internal Medicine who underwent PET/MRI were included. Three PET/MRI patterns were defined: (i) "inflammatory," with positive PET (>liver uptake) and abnormal MRI (stenosis and/or wall thickening); (ii) "fibrous", negative PET (≤liver uptake) and abnormal MRI; and (iii) "normal". Thirteen patients (10 female; median age: 67-years [range: 23-87]) underwent 18 PET/MRI scans. PET/MRI was performed at diagnosis (n = 4), at relapse (n = 7), or during remission (n = 7). Among the 18 scans, eight (44%) showed an inflammatory pattern and three (17%) a fibrous pattern; the other seven were normal. The distribution of the three patterns did not differ between patients with Takayasu arteritis (TA, n = 10 scans) and those with giant cell arteritis (GCA, n = 8 scans). PET/MRI findings were normal in 2/10 (20%) TA scans vs. 5/8 (62%) GCA scans (p = 0.3). Median SUVmax was 4.7 [2.1-8.6] vs. 2 [1.8-2.6] in patients with active disease vs. remission, respectively (p = 0.003). PET/MRI is a new hybrid imaging modality allowing comprehensive and multimodal analysis of vascular wall inflammation and the vascular lumen. This technique offers promising perspectives for the diagnosis and monitoring of LVV

Obstetrical Morbidity Related to Anti-SSA Antibodies: Data from a French Monocentric Retrospective Study

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Role of miRNAs in Normal Endometrium and in Endometrial Disorders: Comprehensive Review

International audienceThe molecular responses to hormonal stimuli in the endometrium are modulated at the transcriptional and post-transcriptional stages. Any imbalance in cellular and molecular endometrial homeostasis may lead to gynecological disorders. MicroRNAs (miRNAs) are involved in a wide variety of physiological mechanisms and their expression patterns in the endometrium are currently attracting a lot of interest. miRNA regulation could be hormone dependent. Conversely, miRNAs could regulate the action of sexual hormones. Modifications to miRNA expression in pathological situations could either be a cause or a result of the existing pathology. The complexity of miRNA actions and the diversity of signaling pathways controlled by numerous miRNAs require rigorous analysis and findings need to be interpreted with caution. Alteration of miRNA expression in women with endometriosis has been reported. Thus, a potential diagnostic test supported by a specific miRNA signature could contribute to early diagnosis and a change in the therapeutic paradigm. Similarly, specific miRNA profile signatures are expected for RIF and endometrial cancer, with direct implications for associated therapies for RIF and adjuvant therapies for endometrial cancer. Advances in targeted therapies based on the regulation of miRNA expression are under evaluation