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[New Onset of Graves' Orbitopathy Following Bendamustine-Rituximab (BR) therapy in a Patient with Chronic Lymphocytic Leukemia: A Case Report and Literature Review].

Graves' orbitopathy (GO) is a progressive autoimmune disorder of visual organ, mostly associated with Graves' disease (GD). Although rituxim … ated T-cell-mediated orbital inflammation, while bendamustine-induced lymphopenia further disrupted immune tolerance. This case illustrates the potential for paradoxical autoimmune activation following BR therapy in a predisposed patient. Clinicians should monitor for GO signs, and symptoms before, during, and after BR therapy in patients with underlying thyroid a …

Impaired T Follicular Regulatory Cell Function and Enhanced T Follicular Helper Cell Activity in Experimental Autoimmune Encephalomyelitis: Mechanistic Insights into CNS Autoimmunity.

Multiple sclerosis is a chronic immune-mediated central nervous system disorder marked by neuroinflammation, demyelination, and neurodegener … . Simultaneously, a marked decrease in FOXP3+ T follicular regulatory-like cells suggested impaired immune tolerance and enhanced autoimmune activity. The infiltration of T follicular helper-like cells was identified as a key driver of inflammation and demyelination in the central nervous system. Additionally, the elevated IL-21 mRNA expression highlighted B cell …

Nanocellulose dysregulated glucose homeostasis in female mice on a Western diet: The role of gut microbiome.

There is currently increased interest in nanocellulose as a food emulsifier and dietary supplement. It was hypothesized that nanocellulose could modulate behaviors and glucose homeostasis in female mice using mechanisms of altered gut microbiome and immune modulation. An initial experiment was conducted with the objective of examining whether three common types of nanocellulose affected the gut microbiome of female C57BL/6 mice on a Western diet. Cellulose nanofibrils (CNF), TEMPO-CNF and cellulose nanocrystals were administered at the physiologically relevant dose of 30 mg/kg/day for 30 days

Whole Exome Sequencing in Children With Autoimmune Hepatitis Identified Mutations in Genes Involved in the mTORC1 Signaling Pathway.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH), a severe immune-mediated liver disease resulting from defective immune tolerance, was thought to be caused by monogenic predisposition with possible external triggers. The development of AIH in monogenic primary immune deficiencies prompted us to search for causative genetic defects in AIH. METHODS: Twenty-two children with AIH were included for whole exome sequencing analysis. Data were analyzed with an in-house software, combined with in silico tools and confirmed by Sanger sequencing. Mechanistic target of rapamycin (mTOR) pathway activation…

A single-cell transcriptomic atlas of the pigtail macaque placenta in late gestation.

The placenta is a complex organ with multiple immune and non-immune cell types that promote fetal tolerance and facilitate the transfer of nutrients and oxygen. The nonhuman primate (NHP) is a key experimental model for studying human pregnancy complications, in part due to similarities in placental structure, which makes it essential to understand how single-cell populations compare across the human and NHP maternal-fetal interface. We constructed a single-cell RNA-Seq (scRNA-Seq) atlas of the placenta from the pigtail macaque ( Macaca nemestrina ) in the third trimester, comprising three dif

Glucocorticoid Receptor-Targeted Nanoliposome for STAT3 Inhibition-Led Myeloid-Derived Suppressor Cell Modulation and Efficient Colon Cancer Treatment.

STAT3 is an important protein responsible for cellular proliferation, motility, and immune tolerance and is hyperactive in colorectal cancer, instigating metastasis, cellular proliferation, migration, as well as inhibition. It helps in proliferation of myeloid-derived suppressor cells (MDSCs), which within the tumor microenvironment (TME) suppress T cells to encourage tumor growth, metastasis, and resistance to immunotherapy, besides playing dynamic role in regulating macrophages within the tumor. Thus, MDSC is a potential target to augment immune surveillance within the TME. Herein, we report…

Investigation of immune checkpoint molecules (CTLA-4, PD-1, PD-L1, Tim-3) expressions in preeclampsia: A comparative study of membranous and soluble forms.

Preeclampsia (PE) is characterized by immune dysfunction, including altered expression levels of multiple immune checkpoints (ICs), which are essential for inducing immune tolerance during pregnancy. While the pivotal role of ICs in PE is well-established, a limited understanding remains of the changes in their various forms, particularly in their membranous and secretory states. This study focused on exploring the probable role of ICs in the pathophysiology of PE via measuring the levels of their transmembrane and soluble forms. Initially, expression levels of transmembrane CTLA-4, PD-1, PD-L…

Mediterranean fever gene variants may prevent the development of lupus nephritis in Japanese patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance, leading to systemic inflammation and organ damage. The Mediterranean fever (MEFV) gene, primarily linked to familial Mediterranean fever (FMF), has been suggested to have a protective role against SLE. However, comprehensive whole-exon analyses of MEFV and research on MEFV or FMF in non-Mediterranean populations, where MEFV exon 10 mutations are relatively rare, are limited. METHODS: We conducted a whole-exon analysis of the MEFV gene in 55 Japanese patients with SLE. Patients we…

Association of NLRP3 and IL-4 VNTR polymorphisms and genetic susceptibility to preeclampsia: A case-control study.

INTRODUCTION: Abnormalities in the maternal immune system and insufficient gestational immune tolerance may significantly contribute to the development of preeclampsia (PE). The NLR family pyrin domain containing 3 (NLRP3) functions as a pattern recognition receptor that identifies pathogen-associated molecular patterns. Interleukin-4 (IL-4) is a potent anti-inflammatory cytokine that modulates the immune response. Therefore, this study aims to elucidate the impact of NLRP3 and IL-4 variable number of tandem repeats (VNTR) polymorphisms on susceptibility to PE. MATERIALS AND METHODS: A total …

Совместное централизованное и периферальное обезвоживание: связанное или совпадение?

Наследственные сенсорные датчики моторного Neurophy (HSMN) 1A и множественный склероз (MS) являются различными демиелионирующими расстройствами, влияющими соответственно на периферийные и центральные нервные системы. Мы представляем пример одновременного возникновения обоих заболеваний, изучения клинического представления, диагностического анализа и потенциального взаимодействия между этими заболеваниями. Презентация дел и клинический подход: 49-летний мужчина с историей зрительного неврата, с прогрессивной онемением, слабостью и сенсорными потерями во всех конечностях на протяжении четырех ле

Совпадение в аннотации оригинала
BACKGROUND: Hereditary Sensory Motor Neuropathy (HSMN) 1A and Multiple Sclerosis (MS) are distinct demyelinating disorders affecting the per … as immune dysregulation. Some evidence suggests that overexpression of PMP22 in HSMN 1A may disturb immune tolerance, possibly triggering autoimmune responses linked to MS. Further research is needed to explore the genetic and autoimmune interplay between these two diseases, expanding our understanding of demyelinating disorders.

Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice.

Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (w/w)) for 24 weeks. The presence of immune complexes was evaluated by i

Identification of novel immune cell signature in gastroesophageal reflux disease: altered mucosal mast cells and dendritic cell profile.

INTRODUCTION: Heartburn pathogenesis in GERD remains incompletely understood. We aimed to identify differences in the immune cell signature and sensory mucosal markers between reflux phenotypes and healthy asymptomatic subjects. METHODS: Thirty-seven patients with heartburn symptoms were phenotyped endoscopically and with objective reflux studies into erosive reflux disease (ERD) (N=10), nonerosive reflux disease (NERD) (N=9), functional heartburn (FH) (N=9), and Barrett's esophagus (BO) (N=9). Bulk mRNA-sequencing(RNA-seq) was conducted on RNA extracted from endoscopic biopsies, and immune c

Donor aKIR genes influence the risk of EBV and CMV reactivation after anti-thymocyte globulin-based haploidentical hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) offers the highest curative potential for patients with hematological malignancies. Complications including infection, graft-versus-host disease (GVHD), and relapse reflect delayed or dysregulated immune reconstitution. After transplantation, NK cells rapidly reconstitute and are crucial for immune surveillance and immune tolerance. NK cell function is tightly regulated by killer immunoglobin-like receptors (KIRs). Previous studies have revealed that donor KIRs, especially some activated KIRs (aKIRs) are closely related to transplant outcomes. Her…

Vitamin D Deficiency in Primary Sjögren's Syndrome: Association with Clinical Manifestations and Immune Activation Markers.

Vitamin D is an agent involved in bone and mineral homeostasis. It has been recognized as a potent immunomodulator. It has immune-enhancing properties, and it induces immune tolerance. Vitamin D deficiency has been shown to be related to the development of autoimmune disorders. Vitamin D deficiency has been observed in patients with rheumatoid arthritis (RA) and it has been shown to be related with disease activity. Vitamin D deficiency has also been found in patients with systemic lupus erythematosus (SLE) and it was shown to be related to disease activity and renal involvement. Vitamin D def…

The AHNAK induces increased IL-6 production in CD4+ T cells and serves as a potential diagnostic biomarker for recurrent pregnancy loss.

Disorganized maternal-fetal immune tolerance contributes to the occurrence of unexplained recurrent pregnancy loss (RPL). AHNAK is a scaffolding protein participating in the regulation of Ca2+ entry into T cells and the pathophysiology of diverse diseases. We performed differential gene expression analysis in decidual immune cells (DICs) isolated from three patients with RPL and from three healthy controls via RNA-sequencing (RNA-seq), which revealed 407 differentially expressed genes (DEGs). Among these DEGs, we underscored the clinical significance of elevated AHNAK mRNA and protein levels i…

Pyroptosis and Its Role in Autoimmune Disease: A Potential Therapeutic Target.

Autoimmune diseases are a group of heterogeneous diseases with diverse clinical manifestations that can be divided into systemic and organ-specific. The common etiology of autoimmune diseases is the destruction of immune tolerance and the production of autoantibodies, which attack specific tissues and/or organs in the body. The pathogenesis of autoimmune diseases is complicated, and genetic, environmental, infectious, and even psychological factors work together to cause aberrant innate and adaptive immune responses. Although the exact mechanisms are unclear, recently, excessive exacerbation o…

Echinococcus granulosus Protoscoleces-Derived Exosome-like Vesicles and Egr-miR-277a-3p Promote Dendritic Cell Maturation and Differentiation.

Cystic echinococcosis, a major parasitic disease caused by Echinococcus granulosus, seriously threatens human health. The excretory-secretory (ES) products of E. granulosus can induce immune tolerance in dendritic cells (DCs) to downregulate the host's immune response; however, the effect of exosomes in the ES products on the DCs has remained unclear. This study showed that E. granulosus protoscoleces-derived exosome-like vesicles (PSC-ELVs) could be internalized by bone marrow-derived dendritic cells (BMDCs), allowing for the delivery of the parasite microRNAs to the BMDCs. Moreover, PSC-ELVs…

COVID-19 and autoimmune diseases.

PURPOSE OF REVIEW: The aim of this study was to evaluate the relationship between infection with SARS-CoV-2 and autoimmunity. RECENT FINDINGS: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome (SARS) associated coronavirus 2 (SARS-CoV-2). Although most of the infected individuals are asymptomatic, a proportion of patients with COVID-19 develop severe disease with multiple organ injuries. Evidence suggests that some medications used to treat autoimmune rheumatologic diseases might have therapeutic effect in patients with severe COVID-19 in

Case Report: Ipilimumab-induced Multisystem Autoimmune-like Toxicities Suggestive of Vogt-Koyanagi-Harada-like Syndrome.

SIGNIFICANCE: The emergence of new cancer therapies has dramatically improved outcomes in metastatic melanoma. Immune checkpoint inhibitors have been the most effective treatment. Although, as a direct consequence of the immune dysregulation induced by them, adverse effects termed immune-related adverse events are observed in more than 60% of the patients. PURPOSE: We describe the clinical presentation of Vogt-Koyanagi-Harada-like syndrome in a patient with concomitant systemic melanoma treatment with ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 blocker. METHODS: This study aime

Case Report: EBV Chronic Infection and Lymphoproliferation in Four APDS Patients: The Challenge of Proper Characterization, Therapy, and Follow-Up.

Activated PI3K-kinase Delta Syndrome (APDS) is an autosomal-dominant primary immunodeficiency (PID) caused by the constitutive activation of the PI3Kδ kinase. The consequent hyperactivation of the PI3K-Akt-mTOR pathway leads to an impaired T- and B-cells differentiation and function, causing progressive lymphopenia, hypogammaglobulinemia and hyper IgM. Patients with APDS show recurrent sinopulmonary and chronic herpes virus infections, immune dysregulation manifestations, including cytopenia, arthritis, inflammatory enteropathy, and a predisposition to persistent non-neoplastic splenomegaly/ly