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Desensitization: Overcoming the Immunologic Barriers to Transplantation.

HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors,

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… Cutting edge: circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production The Journal of Immunology 2015 194 6 2482 2485 10.4049/jimmunol.1401190 2-s2.0-84924588068 25681343 PMC4356730 48 Tanaka T. Narazaki M. Kishimoto T. …

Ligand-based CAR-T cell: Different strategies to drive T cells in future new treatments.

Chimeric antigen receptor (CAR)-based therapies are presented as innovative treatments for multiple malignancies. Despite their clinical success, there is scientific evidence of the limitations of these therapies mainly due to immunogenicity issues, toxicities associated with the infusion of the product, and relapses of the tumor. As a result, novel approaches are appearing aiming to solve and/or mitigate the harmful effects of CAR-T therapies. These include strategies based on the use of ligands as binding moieties or ligand-based CAR-T cells. Several proposals are currently under development

Immunotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with poor prognosis. Surgery, chemotherapy, and radiofrequency ablation are three conventional therapeutic options that will help only a limited percentage of HCC patients. Cancer immunotherapy has achieved dramatic advances in recent years and provides new opportunities to treat HCC. However, HCC has various etiologies and can evade the immune system through multiple mechanisms. With the rapid development of genetic engineering and synthetic biology, a variety of novel immunotherapies have been employed to treat advance

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… CAR NK Cell Therapy for T Follicular Helper Cells. Cell Rep Med (2020) 1(1):100009. doi: 10.1016/j.xcrm.2020.100009 89. Yu M, Luo H, Fan M, Wu X, Shi B, Di S, et al. …

The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management.

Antibody deficiency or hypogammaglobulinemia can have primary or secondary etiologies. Primary antibody deficiency (PAD) is the result of intrinsic genetic defects, whereas secondary antibody deficiency may arise as a consequence of underlying conditions or medication use. On a global level, malnutrition, HIV, and malaria are major causes of secondary immunodeficiency. In this review we consider secondary antibody deficiency, for which common causes include hematological malignancies, such as chronic lymphocytic leukemia or multiple myeloma, and their treatment, protein-losing states, and side

Esid 2014 oral presentations.

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The 45th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Session.

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The Pathophysiology and Treatment of Pyoderma Gangrenosum-Current Options and New Perspectives.

Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. The treatment of PG remains challenging due to the lack of generally accepted therapeutic guidelines. Existing therapeutic methods focus on limiting inflammation through the use of immunosuppressive and immunomodulatory therapies. Recently, several reports have indicated the successful use of biologic drugs an

Chimeric Antigen Receptor T-Cells: An Overview of Concepts, Applications, Limitations, and Proposed Solutions.

Adaptive immunity, orchestrated by B-cells and T-cells, plays a crucial role in protecting the body from pathogenic invaders and can be used as tools to enhance the body's defense mechanisms against cancer by genetically engineering these immune cells. Several strategies have been identified for cancer treatment and evaluated for their efficacy against other diseases such as autoimmune and infectious diseases. One of the most advanced technologies is chimeric antigen receptor (CAR) T-cell therapy, a pioneering therapy in the oncology field. Successful clinical trials have resulted in the appro

Cellular based treatment modalities for unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is unfortunately associated with an overall poor prognosis and high mortality. Early and intermediate stages of HCC allow for treatment with surgical resection, ablation and even liver transplantation, however disease progression warrants conventional systemic therapy. For years treatment options were limited to molecular-targeting medications, of which sorafenib remains the standard of care. The recent development and success of immune checkpoint inhibitors has proven to be a breakthrough in the treatment of

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… CD4+ T helper cells on the other hand further differentiate in the periphery into a variety of subsets ( i.e. , Th1, Th2, Th9, Th17, Th22, regulatory T cells, and T follicular helper cells)[ 100 ]. …

Hematopoietic Tumors

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Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives.

The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a

Adding recombinant AAVs to the cancer therapeutics mix.

Gene therapy is a powerful biological tool that is reshaping therapeutic landscapes for several diseases. Researchers are using both non-viral and viral-based gene therapy methods with success in the lab and the clinic. In the cancer biology field, gene therapies are expanding treatment options and the possibility of favorable outcomes for patients. While cellular immunotherapies and oncolytic virotherapies have paved the way in cancer treatments based on genetic engineering, recombinant adeno-associated virus (rAAV), a viral-based module, is also emerging as a potential cancer therapeutic thr

Cellular mechanisms of multiple myeloma bone disease.

Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulates and proliferates in the bone marrow. MM patients often develop bone disease that results in severe bone pain, osteolytic lesions, and pathologic fractures. These skeletal complications have not only a negative impact on quality of life but also a possible effect in overall survival. MM osteolytic bone lesions arise from the altered bone remodeling due to both increased osteoclast activation and decreased osteoblast differentiation. A dysregulated production of numerous cytokines that can contribut

Promising Experimental Treatments for Lupus Nephritis: Key Talking Points and Potential Opportunities.

Lupus nephritis (LN) is a frequent and serious complication of systemic lupus erythematosus (SLE), impairing patients' quality of life and significantly increasing mortality. Despite optimizing the use of conventional immunosuppressants and other biological drugs, its management remains unsatisfactory. This is mainly due to the heterogeneity of SLE, but also to insufficiently effective treatment regimens and clinical trial limitations (strict criteria, low number of patients included, and side effects). Most clinical trials of new biological therapies have failed to meet their primary endpoint

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… Cell Distance Mapping Identifies Functional T Follicular Helper Cells in Inflamed Human Renal Tissue. Sci Transl Med . 2014;6(230). doi: 10.1126/scitranslmed.3008146 24. Ohmura K. Which is the best SLE activity index for clinical trials? …

Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies.

Neuromyelitis optica (NMO) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by acute optic neuritis (ON) and transverse myelitis (TM). NMO is caused by a pathogenic serum IgG antibody against the water channel aquoporin 4 (AQP4) in the majority of patients. AQP4-antibody (AQP4-ab) presence is highly specific, and differentiates NMO from multiple sclerosis. It binds to AQP4 channels on astrocytes, triggering activation of the classical complement cascade, causing granulocyte, eosinophil, and lymphocyte infiltration, culminating in injury first to as

Energy metabolism in health and diseases.

Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, exten

Эпштейн-Барр Вирус: больше чем просто инфекция.

Хотя вирус Эпштейн-Барр обычно ассоциируется с доброкачественным инфекционным мононуклеозом, он в настоящее время признается в качестве одного из основных движителей сложных иммунопатологических расстройств. Замыкаясь между литическими репликациями и стратегическими программами запоздалости, EBV перепрограммирует биологию B-клеток, чтобы избежать иммунного наблюдения и нарушить гомеостаз. Центральным элементом этого патогенеза является вирусный протеин EBNA1, который приводит к автоматическому иммунитету с помощью молекулярной имитации с принимающими антигенами, включая GlialCAM в множестве ск

Метаболизм триптофана в области диагностических и внегигиенических заболеваний: механизмы, клинические последствия и терапевтические перспективы.

Метаболизм триптофана (Trp) лежит на пересечении питания, микробиотики кишечника, мукосовой иммунологии и системных процессов воспаления, которые играют ключевую роль во многих желудочно-кишечных и внекишечных заболеваниях. Трап представляет собой важнейшую аминокислоту, получаемую с помощью рациона питания. Помимо своей роли в синтезе белка, он метаболизируется по трем основным направлениям: кинуреньиновый путь, серотонин/мелатонин, и микробный метаболизм в кишечнике, ведущий к индолу и связанным с ним производным. Кинуренинский путь представляет собой основной путь деградации Trp и тесно свя

Posttransplant complications: molecular mechanisms and therapeutic interventions.

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation.

The impact of the gut microbiome on tumor immunotherapy: from mechanism to application strategies.

Immunotherapy is one of the fastest developing areas in the field of oncology. Many immunological treatment strategies for refractory tumors have been approved and marketed. Nevertheless, much clinical and preclinical experimental evidence has shown that the efficacy of immunotherapy in tumor treatment varies markedly among individuals. The commensal microbiome mainly colonizes the intestinal lumen in humans, is affected by a variety of factors and exhibits individual variation. Moreover, the gut is considered the largest immune organ of the body due to its influence on the immune system. In t

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… During homeostasis, Akkermansia muciniphila (AKK) can induce T follicular helper cells in Peyer’s patches to produce an IgG1 antibody-dependent immune response [ 78 ]. …