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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.

Коэффициенты транскрипции заболеваний экзокринной и эндокринной поджелудочной железы: эффекты, механизмы и клинические последствия.

Белки BTB и CNC (BACH) BACH1 и BACH2 являются высоко сберегаемыми транскрипционными репрессорами, которые оказывают свое воздействие, образуя гетеродимеры с маленькими мускулопоневрологическими фибросаркома (MAF). BACH1 повсеместно выражается и выполняет функции, конкурируя с эритроидом ядерного фактора 2-like 2 (NRF2) для привязки к MAF. Ограничивая транскрипцию гема кислородазы 1 (В тыс.HO-1/HMOX1), BACH1 препятствует выражению генов, участвующих в реакции клеточного окислительного стресса. Выражение BACH2 в основном ограничивается иммунными клетками как в врожденных, так и в адаптивных отсе

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… This establishes a negative feedback loop for IFN-α signaling in β-cells, preventing the overexpression of proinflammatory chemokines (e.g., CXCL10) and of antigen presentation via the major histocompatibility complex HLA. …

Неудовлетворение влияния полиморфизма HHEX rs7923837 на патогенез с множественным склерозом.

One (MS) риск полиморфизма, rs7923837, карты вблизи гена HHEX (гематопоэтический гомеобокс). Этот вариант также связан с типом 2 Уязвимость диабета и уровень триглицерида, что говорит о его участии в метаболике. HHEX играет важную роль в качестве негативного регулятора воспалительных генов в микроглии. Сообщалось о взаимных репрессиях между HHEX и BCL6, еще один предполагаемый фактор риска в РС. Настоящее исследование свидетельствует о статистически значимых более низких уровнях содержания HHEX mRNA в лимфоцитах пациентов с НР по сравнению с уровнем контроля, что свидетельствует о аналогичной

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… For decades, the major histocompatibility complex (MHC) was the only genetic factor related to MS susceptibility. More recently, genome-wide association studies (GWAS) allowed the identification of 233 MS risk variants accounting for around 50% of the total MS heritability [ 3 ]. …

Allogeneic and other innovative chimeric antigen receptor platforms.

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… Flu: Fludarabine; Cy: Cyclophosphamide; MHC: Major histocompatibility complex’ HLA-E: Human leukocyte antigen E; PD-1: Programmed cell death protein 1 Prior to CAR T-cell infusion, a lymphodepleting conditioning regimen of fludarabine (Flu) and cyclophosphamide (Cy) is typically administered. … Initial efforts to prevent T-cell mediated rejection included knockdown of beta-2 microglobulin to prevent major histocompatibility complex (MHC) class I expression 53,54 and rejection by CD8 + T-cells. …

Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity.

BACKGROUND: Peripheral blood-derived natural killer (NK) cells spontaneously lyse tumor cells without prior sensitization. However, NK cells in peripheral blood (PBNK cells) are in a resting state and exhibit inhibitory phenotypes and impaired cytotoxicity. Thus, strengthening the cytotoxic effector function of PBNK cells and improving NK cell expansion in vitro for a convenient allogeneic therapy are essential. MATERIALS AND METHODS: Pure cytokine activation and expansion of NK cells (super NK [SNK]) from peripheral blood mononuclear cells were studied. Markers of activated and inhibited NK

Alpha-lipoic acid as a trigger of insulin autoimmune syndrome: Current evidence, a case-based approach, diagnostic pitfalls, and practical management.

Insulin autoimmune syndrome (IAS), also known as Hirata disease, is a rare immune-mediated cause of endogenous hyperinsulinemic hypoglycemia characterized by circulating insulin autoantibodies (IAAs). It typically develops in individuals without prior exposure to exogenous insulin. Although IAS has been associated with viral infections and, less commonly, with autoimmune and hematologic disorders, medications and dietary supplements are considered the most frequent precipitating factors. Sulfhydryl-containing compounds are the most commonly implicated triggers. Methimazole represents the class

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… The resulting insulin-derived peptides can subsequently be presented by Major Histocompatibility Complex (MHC) class II molecules, particularly in genetically susceptible individuals carrying specific HLA alleles such as HLA-DRB1*04:06. … Histocompatibility Complex Mycophenolate mofetil Medical nutrition therapy Magnetic resonance imaging Nutrition, Novel Foods and Food Allergens Oral Glucose Tolerance Test Polyethylene glycol Positron emission tomography/computed tomography Phosphoinositide 3-kinase Proton pump inhibitors …

Immunotherapy in chronic lymphocytic leukemia: advances and challenges.

Chronic lymphocytic leukemia (CLL) is characterized as a clonal proliferation of mature B lymphocytes with distinct immunophenotypic traits, predominantly affecting the middle-aged and elderly population. This condition is marked by an accumulation of lymphocytes within the peripheral blood, bone marrow, spleen, and lymph nodes. The associated immune dysregulation predisposes CLL patients to a higher risk of secondary malignancies and infections, which significantly contribute to morbidity and mortality rates. The advent of immunotherapy has revolutionized the prognosis of CLL, advancing treat

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… They exhibit potent anti-tumor activity and, unlike T cells, do not have Major Histocompatibility Complex (MHC) restrictions. They exhibit potent anti-tumor activity and, unlike T cells, do not have Major Histocompatibility Complex (MHC) restrictions. … Histocompatibility Complex Multiple Myeloma Monomethyl Auristatin E Minimal Residual Disease Multiple Sclerosis Non-Hodgkin Lymphoma Natural Killer Objective Response Rate Overall Survival Pyrrolobenzodiazepine Dimer Primary Cutaneous Anaplastic Large Cell Lymphoma Programmed Death-1 Programmed …

Комплексный метаанализ транскриптомов астроцитов человека показывает, что в ответ на подстрекательские и иммунные стимулы потенциальные признаки повторяются.

Астроциты являются ключевыми регуляторами подстрекательской и иммунной реакции в центральной нервной системе, особенно в патологических условиях. Мы проводили систематический поиск баз данных НКОИ по ГЭП и ЭНА в целях выявления транскриптивных исследований стимулируемых астроцитов. Этот метаанализ объединяет 11 наборов данных RNA-Seq, охватывающих в общей сложности 153 пробы (91 стимулируемый и 62 средства контроля), подвергающиеся воздействию провоспалительных стимулов, таких, как цитокины (TNF-α, IL-6 и IL-1β), пальмовая кислота и патогены, такие, как SARS-COV-2 и Borrelia burborferi. Благод

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… Specifically, they induce the expression of major histocompatibility complex class II (MHC-II) molecules and costimulatory signals, aiding peripheral immune cell recruitment ( Le Thuc and García-Cáceres, 2024 ; Xie and Yang, 2015 ). … Previous studies have described enrichment in pathways related to immune system activation, antiviral innate immunity, major histocompatibility complex, cytokine/interferon signaling, and the inflammatory response through TNF signaling, NOD-like receptor, and NF-κB signaling in astrocytes exposed to …

Протекционный субъект PSMD1 является ключевой терапевтической целью в множестве миеломы.

Мы пришли к выводу, что PSMD1 - ключевой субъект протеиновой регуляционной частицы 19S - был чрезмерно экспрессирован и коррелировал с плохим прогнозом в множестве миеломы (ММ). Генетическое истощение PSMD1 снизило жизнеспособность раковых клеток, вызвало поликутилизированное накопление белка и способствовало апоптозу. Протеомический анализ показал активацию иммунных путей, что свидетельствует о потенциале иммунной модуляции. Нацеливание PSMD1 на незначительную поражающую РНК (SIRNA), доставляемую через липидные наночастицы (LNPs), уменьшило рост опухоли в линиях клеток MM и первичных проб пац

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… Consistent with cytokine-driven immune activation, surface expression of major histocompatibility complex class I (HLA-ABC) and class II (HLA-DR and HLA-DQ) molecules was significantly elevated in PSMD1-depleted cells ( supplemental Figure 4 D). … Major histocompatibility complex class molecules play a critical role in antigen presentation and the subsequent activation of CD4 + and CD8 + T cells. …

Унификация модели множественного склероза.

Множественный склероз (MS) представляет собой сложное нейродегенеративное расстройство с неразрешенной причиной, ставшей предметом интенсивных исследований. Для разъяснения курса болезни были предложены различные предлагаемые модели. Первостепенные механизмы, как предполагается, основываются на автоматическом иммунитете, в том числе с помощью вирусного имитации эпитопов, хотя и были описаны трудности с классической моделью автономного иммунитета для MS. Одна предыдущая идея, которая включает в себя рассмотрение вирусной самореактивности, заключается в том, что реактивированный вирус HHV-6A мож

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… Abbreviations Central nervous system Cerebrospinal fluid Experimental autoimmune encephalomyelitis Epstein–Barr nuclear antigen 1 Epstein–Barr virus Hepatitis C virus Human herpesvirus-6A Major histocompatibility complex Multiple sclerosis Oligoclonal band Primary progressive multiple sclerosis …

Immune checkpoint blockade in cancer treatment: a double-edged sword cross-targeting the host as an "innocent bystander".

Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific "immune-related adverse events" (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique "innocent bystander" effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include

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… In the ‘‘two-signal’’ model of T-cell activation, antigen-specific T-cell activation needs two signals between T-cells and antigen presenting cells (APCs): the first signal involves the presentation of an antigen to a T-cell receptor (TCR) by a major histocompatibility complex (MHC) molecule on APCs. … Figure 1 The ‘‘two-signal’’ model of T-cell activation, first requiring the interaction of T-cell receptor (TCR) with a major histocompatibility complex (MHC) molecule expressed by antigen presenting cells (APCs). …

Application of GPRC5D Targeting Therapy in Relapsed Refractory Multiple Myeloma.

BackgroundAs a rapidly developing therapeutic method, targeted therapy plays an important role in the treatment of multiple myeloma. In recent years, mature B cell antigen-targeting therapy has brought new hope for patients with refractory/relapsed disease. While an increasing number of patients with relapse are exposed to this type of drug, changing the therapeutic target may be an effective strategy for patients with relapse/refractory multiple myeloma.ObjectivesThe expression of G protein-coupled receptor, class C Group 5 member D (GPRC5D), on the surface of myeloma tumor cells makes it a p

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… histocompatibility complex multiple myeloma minimal residual disease matched unrelated donor hematopoietic stem cell transplantation natural killer no response overall response rate overall survival progression‐free survival partial response relapsed/refractory multiple myeloma serious adverse … BsAb‐induced T‐cell‐mediated tumolysis, independent of antigen recognition by major histocompatibility complex molecules, antigen‐presenting cells, or costimulatory molecules, is an important treatment option for RRMM. …

Bispecific and multispecific immune engagers for redirecting innate and adaptive immunity against hematologic cancers.

Bispecific antibodies (BsAbs) and multispecific antibodies (MsAbs) represent a transformative class of immunotherapeutics in oncology. These engineered molecules possess the unique ability to simultaneously target two or more distinct antigens, thereby facilitating precise immune cell engagement and disrupting multiple signaling pathways. This comprehensive review focuses on their pivotal role in redirecting both innate (natural killer cells, phagocytes) and adaptive (T cells) immunity, with a particular emphasis on their application against hematologic cancers. Significant clinical successes,

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… A critical advantage of T-cell-redirecting engagers is their ability to induce T-cell activation and tumor killing in a major histocompatibility complex (MHC)-independent manner [ 9 , 10 ]. … A critical advantage, particularly for T-cell-redirecting engagers, is their ability to induce T-cell activation and tumor killing in a major histocompatibility complex (MHC)-independent manner [ 9 , 49 ]. …

Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition.

γδ T cells are among the first line of defense in the immune system, playing a crucial role in bridging innate and adaptive immunity. Although γδ T cells are crucial for tumor immune surveillance, the complete mechanism by which γδ T cell receptors identify molecular targets in target cells remains unknown. Target cells can produce phosphoantigens (PAgs) via the mevalonate pathway or the methylerythritol phosphate pathway. The BTN3A1-BTN2A1 complex undergoes conformational changes in its extracellular domains upon binding to PAgs, leading to Vγ9Vδ2 T cell recognition. However, the structural b

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… While αβ T cells primarily recognize the antigens presented by major histocompatibility complex (MHC) molecules [ 3 ], Vγ9Vδ2 T cells generally identify tumors without MHC, often via butyrophilin (BTN) complexes on tumor cell surfaces [ 4 ]. … The V beta complementarity determining region 1 of a major histocompatibility complex (MHC) class I-restricted T cell receptor is involved in the recognition of peptide/MHC I and superantigen/MHC II complex J. Exp. Med. 1994 179 1087 1097 10.1084/jem.179.4.1087 8145032 PMC2191438 4. Sandoz P.A. …

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

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… The T-cell receptor (TCR) recognizes peptide antigens presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. … One of the most well-known genetic factors associated with autoimmune diseases is the major histocompatibility complex (MHC). Located on chromosome 6, the MHC plays a critical role in the immune system’s recognition of self- and non-self-molecules. …

Role of Proteasomes in Inflammation.

The ubiquitin-proteasome system (UPS) is involved in multiple cellular functions including the regulation of protein homeostasis, major histocompatibility (MHC) class I antigen processing, cell cycle proliferation and signaling. In humans, proteasome loss-of-function mutations result in autoinflammation dominated by a prominent type I interferon (IFN) gene signature. These genomic alterations typically cause the development of proteasome-associated autoinflammatory syndromes (PRAAS) by impairing proteasome activity and perturbing protein homeostasis. However, an abnormal increased proteasomal

Case Report: Kidney Transplantation in a Patient With Acquired Agammaglobulinemia and SLE. Issues and Challenges.

Lupus nephritis in the context of Systemic Lupus Erythematosus (SLE) is characterized by an unpredicted course with remissions and flare-ups. Among others, it remains a significant cause of end-stage kidney disease (ESKD) in relatively young patients. Therapeutic regimens with newer immunosuppressive agents have been introduced in order to control SLE clinical manifestations more efficiently and limit organ damage induced by immune complex formation and sustained inflammation. Treatment is usually long-term, and the cumulative impact of immunosuppression is expressed through the increased freq

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… The key target for immunosuppressive treatments in solid organ transplantation is the major histocompatibility complex (MHC) or HLA complex. …

The prevention of disease relapse after allogeneic hematopoietic cell transplantation in acute myeloid leukemia.

Disease relapse represents by far the most frequent cause of hematopoietic cell transplantation (HCT) failure. Patients with acute leukemia suffering relapse after HCT have limited conventional treatment options with little possibility of cure and represent, de facto, suitable candidates for the evaluation of novel cellular and biological-based therapies. Donor lymphocyte infusions (DLI) has been one of the first cellular therapies adopted to treat post HCT relapse of acute leukemia patients and still now, it is widely adopted in preemptive and prophylactic settings, with renewed interest for

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… Immunomodulatory effects induced by cytotoxic T lymphocyte antigen 4 immunoglobulin with donor peripheral blood mononuclear cell infusion in canine major histocompatibility complex-haplo-identical non-myeloablative hematopoietic cell transplantation. …

Insights Into the Role of Vitamin D as a Biomarker in Stem Cell Transplantation.

Vitamin D was discovered 100 years ago and since then multiple studies have consistently proved its effect on bone health and mineral metabolism. Further research has also explored its so-called "non-classical" biological effects, encompassing immune regulation and control of cell proliferation and differentiation. Vitamin D downregulates pro-inflammatory immune cells and subsequently their cytokine production, while enhancing the anti-inflammatory subsets, thus mediating inflammation and fostering a more tolerogenic environment. Its biological action is exerted through the vitamin D receptor,

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… Furthermore, vitamin D downregulates the expression of MHC (major histocompatibility complex) class II on the macrophage surface, hindering T-cell activation ( 41 ) and decreasing the pool of circulating CD16 + monocytes and their secretion of TNF-α ( 60 ). … Vit D, vitamin D; +, activation; –, inhibition; MHC II, major histocompatibility complex class II; APCs, antigen presenting cells; Th2, T helper lymphocytes 2; IL, interleukin; Treg, regulatory T cells; TNF-α, tumor necrosis factor α; IFN-γ, interferon γ; CD8 + and CD4 + , T lymphocytes CD8 + and CD4 …

Hematopoeitic Cell Transplantation and CAR T-Cell Therapy: Complements or Competitors?

Allogeneic hematopoietic cell transplantation (allo-HCT) and chimeric antigen receptor T cell (CAR T) therapy are the main modalities of adoptive cellular immunotherapy that have widely permeated the clinical space. The advent of both technologies revolutionized treatment of many hematologic malignancies, both offering the chance at sustained remissions for patients who would otherwise invariably succumb to their diseases. The understanding and exploitation of the nonspecific alloreactivity of allo-HCT and the graft-versus-tumor effect is contrasted by the genetically engineered precision of C

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… Numerous studies of graft rejection and GVHD in the context of UCART have demonstrated the role of the T cell receptor (TCR) in recognizing non-self major histocompatibility complex (MHC) molecules and/or MHC molecules complexed with peptides, conferring alloreactivity ( 143 – 145 ). …