Sjögren\'s disease (SjD) is a systemic autoimmune disorder characterized by a triad of key symptoms affecting almost all patients (salivary and lacrimal dryness, pain and fatigue) and extra-glandular systemic involvement affecting one to two-thirds of patients. Over the past decade, knowledge of the epidemiology, classification criteria, assessment of systemic activity and symptoms presented by patients has grown. In addition, advances in understanding the pathophysiology of SjD have enabled a more targeted therapeutic approach. Current management of SjD is based on EULAR treatment guidelines. But since these recommendations, new drugs targeting specific pathophysiological pathways of the disease, and essentially B lymphocyte activation, have shown efficacy in phase 2 trials. In this review, we will summarize the available evidence on systemic therapies, including: 1. advances in outcome assessment, 2. current evidence on targeted disease-modifying therapies and biologic drugs targeting primarily B lymphocytes, 3. an overview of promising drugs being tested in ongoing trials.
UNASSIGNED: Maladie de Sjögren : de la physiopathologie aux avancées thérapeutiques.
UNASSIGNED: La maladie de Sjögren (SjD) est une maladie auto-immune systémique caractérisée par une triade de symptômes clés affectant presque tous les patients (sécheresse salivaire et lacrymale, douleur et fatigue) et une atteinte systémique extra-glandulaire pouvant toucher un à deux tiers des patients. Au cours de la dernière décennie, les connaissances sur l’épidémiologie, les critères de classification, l’évaluation de l’activité systémique et des symptômes présentés par les patients se sont développés. En outre, les progrès réalisés dans la compréhension de la physiopathologie du SjD ont permis d’adopter une approche thérapeutique plus ciblée. La prise en charge actuelle du SjD s’appuie sur les recommandations thérapeutiques de l’EULAR. Mais depuis ces recommandations, de nouveaux médicaments ciblant des voies physiopathologiques spécifiques de la maladie, et essentiellement l’activation du lymphocyte B, ont montré une efficacité dans des essais de phase 2. Dans cette revue, nous résumerons les données factuelles disponibles sur les traitements systémiques, y compris : 1. les progrès dans l’évaluation des résultats, 2. les preuves actuelles concernant les traitements de fond ciblés et les biomédicaments ciblant essentiellement les lymphocytes B, 3. une vue d’ensemble des médicaments prometteurs testés dans les études en cours.

Despite advances in the genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein-level information. Nowadays breast cancer clinical treatment selection is based on the immunohistochemical (IHC) determination of four protein biomarkers: Estrogen Receptor 1 (ESR1), Progesterone Receptor (PGR), Human Epidermal Growth Factor Receptor 2 (HER2), and proliferation marker Ki-67. The prognostic correlation of tumor-infiltrating T cells has been widely studied in breast cancer, but tumor-infiltrating B cells have not received so much attention. We aimed to find a correlation between immunohistochemical results and a proteomic approach in measuring the expression of proteins isolated from B-cell lymphocytes in peripheral blood samples. Shotgun proteomic analysis was chosen for its key advantage over other proteomic methods, which is its comprehensive and untargeted approach to analyzing proteins. This approach facilitates better characterization of disease-associated changes at the protein level. We identified 18 proteins in B cell lymphocytes with a significant fold change of more than 2, which have promising potential to serve as breast cancer biomarkers in the future.

Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, causing pain and infertility. Despite the rather unclear etiopathogenesis, recent studies suggest the involvement of the immune system in the development and progression of endometriosis. The role of the PD-1/PD-L1 axis in the modulation of the immune response in this disease seems to be particularly interesting. This preliminary study aimed to investigate the expression of PD-1 and PD-L1 on T and B lymphocytes in peripheral blood in patients with endometriosis to assess their potential impact on disease progression. Our study involved peripheral blood samples from 80 patients diagnosed with endometriosis and 20 healthy women as a control group were analyzed. Flow cytometry was used to assess the expression of PD-1 and PD-L1 on T and B lymphocytes, and enzyme-linked immunosorbent assays were used to assess their soluble forms in serum and peritoneal fluid.in our research we observe significantly higher expression of PD-1 and PD-L1 on T and B lymphocytes was found in patients with endometriosis compared to the control group. Higher expression of both tested molecules correlated with the stage of endometriosis. The results of our preliminary studies indicate a potential role of the PD-1/PD-L1 axis in the modulation of the immune response in endometriosis. Modified expression of these proteins may contribute to immune evasion by ectopic tissues, supporting their survival and proliferation. These findings suggest that targeting PD-1/PD-L1 could be explored as a therapeutic option for the treatment of endometriosis, though further research with larger sample sizes is necessary to confirm these results and clarify the role of PD-1/PD-L1 in the pathogenesis of the disease.

Asthma is a complex trait, often associated with atopy. The genetic contribution has been evidenced by familial occurrence. Genome-wide association studies allowed for associating numerous genes with asthma, as well as identifying new loci that have a minor contribution to its phenotype. Considering the role of environmental exposure on asthma development, an increasing amount of literature has been published on epigenetic modifications associated with this pathology and especially on DNA methylation, in an attempt to better understand its missing heritability. These studies have been conducted in different tissues, but mainly in blood or its peripheral mononuclear cells. However, there is growing evidence that epigenetic changes that occur in one cell type cannot be directly translated into another one. In this review, we compare alterations in DNA methylation from different cells of the immune system and of the respiratory tract. The cell types in which data are obtained influences the global status of alteration of DNA methylation in asthmatic individuals compared to control (an increased or a decreased DNA methylation). Given that several genes were cell-type-specific, there is a great need for comparative studies on DNA methylation from different cells, but from the same individuals in order to better understand the role of epigenetics in asthma pathophysiology.

暂无摘要。

Systemic lupus erythematous is a chronic autoimmune disease characterized by the inflammation of several tissues and the production of auto-antibodies directed against nuclear antigens. Complex genetic disorders and environmental factors are at the origin of the disease but the precise cause of the auto-immune process is still unknown. Both innate and adaptive immune systems are involved. Apoptosis seems to be the main source of auto-antigens. The interactions between apoptotic cells, dendritic cells and lymphocytes activate the production of pathogenic antibodies and T lymphocytes. Amplification loops sustain the auto-immune process and the chronic inflammation. Several data point out B-lymphocytes and several cytokines involved in their homeostasis as new promising therapeutic targets.

The view that B lymphocytes are pathogenic in diverse pathological settings is supported by the efficacy of B-cell-ablative therapy in lymphoproliferative disorders, autoimmune diseases and graft rejection. Anti-B-cell antibodies (Abs) directed against CD20 have therefore been generated, and of these, rituximab was the first anti-CD20 monoclonal Ab (mAb) to be applied. Rituximab-mediated apoptosis, complement-dependent cytotoxicity and Ab-dependent cellular cytotoxicity differ from one disease to another, and, for the same disease, from one patient to another. This knowledge has prompted the development of new anti-CD20 mAbs in the hope of improving B-cell depletion. The inclusion of CD20/anti-CD20 complexes in large lipid rafts (LRs) enhances the results of some, but not all, anti-CD20 mAbs, and it may be possible to include smaller LRs. Lipid contents of membrane may be abnormal in malignant B-cells, and could explain resistance to treatment. The function of these mAbs and the importance of LRs warrant further investigation. A detailed understanding of them will increase results for B-cell depletion in lymphoproliferative diseases.