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Биомаркеры CSF активации B-клеток в множестве склерозов: клиническая перспектива.

Роль клеток B в патофизиологии множественных склерозов (MS) выходит за рамки синтеза антител, включая также модуляцию T лимфоцитов и миелиоидных клеток. Активация B-клеток в рамках центральной нервной системы связана с высвобождением различных антител, цитокинов и химокинов, которые измеряются в биофильтрах, и тем самым служат биомаркерами иммунных процессов, отвечающих за MS. С этой целью биомаркетная характеристика заболевания посредством сочетания хорошо зарекомендовавших себя маркеров, например, иммуноглобулин (Ig) G-индекс (Ig) G, олиголональные полосы Ig, свободные световые цепи Ig с нов

Therapeutic Antibodies in Cancer Treatment in the UK.

The growing understanding of the molecular mechanisms of carcinogenesis accelerated the development of monoclonal therapeutic antibodies to specifically target multiple cancer pathways. Recombinant protein therapeutics now constitute a large proportion of yearly approved medicines. Oncology, autoimmune diseases and to a smaller degree the prophylaxis of organ transplant rejection are their main application areas. As of the date of this review, 37 monoclonal antibody products are approved for use in cancer treatments in the United Kingdom. Currently, the antibody therapeutics market is dominate

Taming renal inflammation: signaling pathways and therapeutic advances in lupus nephritis.

Lupus nephritis (LN), a serious complication of systemic lupus erythematosus (SLE), involves complex immune dysregulation that leads to chronic renal inflammation and progressive tissue damage. Despite decades of use of standard immunosuppressive therapy, treatment responses remain variable, and many patients experience relapses or develop end-stage renal disease. This review synthesizes emerging insights into the immunopathogenesis of LN, drawing on studies from single-cell transcriptomics, signaling pathway analyses and renal tissue immunology. It examines the role of both innate and adaptiv

CAR T-Cell Therapy for Cancer: Latest Updates and Challenges, with a Focus on B-Lymphoid Malignancies and Selected Solid Tumours.

Although exponential progress in treating advanced malignancy has been made in the modern era with immune checkpoint blockade, survival outcomes remain suboptimal. Cellular immunotherapy, such as chimeric antigen receptor T cells, has the potential to improve this. CAR T cells combine the antigen specificity of a monoclonal antibody with the cytotoxic 'power' of T-lymphocytes through expression of a transgene encoding the scFv domain, CD3 activation molecule, and co-stimulatory domains. Although, very rarely, fatal cytokine-release syndrome may occur, CAR T-cell therapy gives patients with ref

Comparative single-cell multiplex immunophenotyping of therapy-naive patients with rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus shed light on disease-specific composition of the peripheral immune system.

INTRODUCTION: Systemic autoimmune diseases (SADs) are a significant burden on the healthcare system. Understanding the complexity of the peripheral immunophenotype in SADs may facilitate the differential diagnosis and identification of potential therapeutic targets. METHODS: Single-cell mass cytometric immunophenotyping was performed on peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) and therapy-naive patients with rheumatoid arthritis (RA), progressive systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). Immunophenotyping was performed on 15,387,165 CD45+

Role of Non-Coding RNAs in the Development of Targeted Therapy and Immunotherapy Approaches for Chronic Lymphocytic Leukemia.

In the past decade, novel targeted therapy approaches, such as BTK inhibitors and Bcl2 blockers, and innovative treatments that regulate the immune response against cancer cells, such as monoclonal antibodies, CAR-T cell therapy, and immunomodulatory molecules, have been established to provide support for the treatment of patients. However, drug resistance development and relapse are still major challenges in CLL treatment. Several studies revealed that non-coding RNAs have a main role in the development and progression of CLL. Specifically, microRNAs (miRs) and tRNA-derived small-RNAs (tsRNAs

Secondary myeloid neoplasms after CD19 CAR T therapy in patients with refractory/relapsed B-cell lymphoma: Case series and review of literature.

BACKGROUND: Several chimeric antigen receptor T cells (CAR T) targeting CD19 have induced profound and prolonged remission for refractory/relapsed (R/R) B-cell lymphoma. The risk of secondary malignancies, especially myeloid neoplasms, is of particular concern in the CAR T community, which still remains unclear. METHODS: Four patients with R/R B-cell lymphoma after CD19 CAR T therapy diagnosed with secondary myeloid neoplasms (SMN) from 2 hospitals in eastern China were presented, including 3 with myelodysplastic syndrome (MDS) and 1 with acute myeloid leukemia (AML). Using single-cell RNA se

Immunotherapy and CRISPR Cas Systems: Potential Cure of COVID-19?

The COVID-19 has plunged the world into a pandemic that affected millions. The continually emerging new variants of concern raise the question as to whether the existing vaccines will continue to provide sufficient protection for individuals from SARS-CoV-2 during natural infection. This narrative review aims to briefly outline various immunotherapeutic options and discuss the potential of clustered regularly interspaced short palindromic repeat (CRISPR Cas system technology against COVID-19 treatment as specific cure. As the development of vaccine, convalescent plasma, neutralizing antibodies

Совпадение в полном тексте источника
… Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19 . Cell . 2020 ; 183 ( 1 ): 143 – 157.e13 . PMID: 32877699; PMCID: PMC7437499 . doi: 10.1016/j.cell.2020.08.025 32877699 PMC7437499 41. Chen L , Zody MC , Di Germanio C , et al. …

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

Understanding Autoimmunity: Mechanisms, Predisposing Factors, and Cytokine Therapies.

Autoimmunity refers to an organism's immune response against its own healthy cells, tissues, or components, potentially leading to irreversible damage to vital organs. Central and peripheral tolerance mechanisms play crucial roles in preventing autoimmunity by eliminating self-reactive T and B cells. The disruption of immunological tolerance, characterized by the failure of these mechanisms, results in the aberrant activation of autoreactive lymphocytes that target self-tissues, culminating in the pathogenesis of autoimmune disorders. Genetic predispositions, environmental exposures, and immun

Нейроинфламмация в нейродегенеративных заболеваниях: сосредоточение внимания на посредничестве лимфоцитов T.

Нейродегенеративные заболевания представляют собой группу заболеваний, характеризующихся постепенным ухудшением центральной нервной системы, что приводит к снижению когнитивных, моторных и эмоциональных способностей пациентов. Нейроинфламмация играет важную роль в развитии этих заболеваний. Вместе с тем исследования терапевтических подходов к целенаправленной борьбе с нейроинфламмацией носят ограниченный характер. Все шире признается роль лимфоцитов, которые являются важнейшими посредниками адаптивной иммунной реакции, в нейродегенеративных заболеваниях. В настоящем обзоре основное внимание уд

Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management.

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, a

Многоомичные биомаркеры, связанные с множественным склерозом: от менделианской случайности до прогнозирования наркотиков.

В настоящее время лечение и профилактика множественных склерозов (МС) по-прежнему сталкиваются с серьезными проблемами. Одним из важнейших методов проведения исследований в рамках реализации новых терапевтических стратегий стал менделийский анализ случайности (МСР). Соответственно, мы предполагаем, что существует причинно-следственная связь между генетическими вариантами конкретных плазменных белков и MS с помощью механизмов MR и что ключевые терапевтические цели можно точно определить путем интеграции многомерных аналитических подходов. В этом исследовании мы разработали всеобъемлющую аналити

Интратективный иммуноглобулин А Обобщение в множестве склероза: от биологических аспектов к клинической значимости.

Интратекальский иммуноглобулин А (IgA) синтез в множестве склерозов (MS) давно не получал достаточного внимания, несмотря на потенциальное значение патогенеза и прогноза заболеваний. Наличие доброкачественных плазменных клеток IgA в повреждениях MS и вдоль поврежденных аксонов свидетельствует о роли в патогенезе болезней. Имеющиеся клинические данные о потенциальной позитивной или негативной прогнозируемой роли являются скудными и неточными. Вместе с тем последние наблюдения свидетельствуют о переходе от кишечника к центральной нервной системе (КНС) в экспериментальные аутоиммунные энцефалитны

Компендиум одноклеточных человеческих цереброспинных жидкостей идентифицирует популяции иммунных клеток, связанные с болезнями.

Одноклеточная транскриптомика, применяемая к цереброспинной жидкости (CSF) для разъяснения патофизиологии неврологических заболеваний, позволила получить лишь предварительную характеристику иммунных клеток CSF. CSF образуется из ткани центральной нервной системы (CNS) и граничит с ней, что позволяет проводить полный учет типов клеток наряду с их относительным изобилием и иммунологическими характеристиками, имеющими отношение к заболеваниям CNS. Используя методы интеграции, применяемые к общедоступным наборам данных в сочетании с нашими собственными исследованиями, мы подготовили компендиум, со

The Continuum of Thyroid Disorders Related to Immune Checkpoint Inhibitors: Still Many Pending Queries.

BackgroundUntil more data are available to shed light on the thyroid disorders related to immune checkpoint inhibitors (ICPi) implemented for the treatment of hematological malignancies, the decision-making is guided by pertinent data derived mostly from solid tumors.MethodsThe present review provides a comprehensive and updated overview of the thyroid disorders related to ICPi, namely to inhibitors of cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death (PD) 1 (PD-1), and the ligand of the latter (PD-L1).ResultsWith the increasing recognition of ir thyroid disorders, many outstand

IL6-receptor antibody tocilizumab as salvage therapy in severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a retrospective analysis.

Chronic graft-versus-host disease (cGvHD) remains the most relevant factor affecting survival after allogeneic hematopoietic stem cell transplantation (alloHSCT). Besides corticosteroids (and ibrutinib in the USA), there is no established therapy for cGvHD. Tocilizumab, a humanized IgG1 IL6-receptor antibody, has shown efficacy in acute GvHD and cGvHD. We retrospectively analyzed the efficacy and safety of tocilizumab for the treatment of advanced cGvHD. Eleven patients with severe steroid refractory cGvHD (median age 49; range 21-62 years) that received at least two prior lines of therapy for

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Chromatin modifiers in human disease: from functional roles to regulatory mechanisms.

The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by reg

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer.

PurposeAdoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.Materials and methodsMultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally r