Polymorphic Variants in the Vitamin D Receptor and Clinical Parameters of Rheumatoid Arthritis Patients Undergoing Anti-TNF Treatment.

Vitamin D levels have been related to the severity and progression of various autoimmune disorders. In this study, we aimed to investigate the impact of genetic variability in the vitamin D receptor (VDR) gene on disease susceptibility and progression in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. The study comprises 121 RA patients subjected to anti-TNF therapy genotyped for four VDR polymorphic variants: rs1544410 (I), rs2228570 (I), rs731236 (I), and rs7975232 (I).

Characterisation of LGP2 complex multitranscript system in humans: role in the innate immune response and evolution from non-human primates.

Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), including RIG-I, MDA5 and LGP2, recognize viral RNA to mount an antiviral interferon (IFN) response RLRs share three different protein domains: C-terminal domain, DExD/H box RNA helicase domain, and an N-terminal domain with two tandem repeats (CARDs). LGP2 lacks tandem CARD and is not able to induce an IFN response. However, LGP2 positively enhances MDA5 and negatively regulates RIG-I signaling.

Combined Molecular Mismatch Approaches to Predict Immunological Events Within the First Year After Renal Transplantation.

Several molecular mismatch assessment approaches exist, but data on their combined use are limited. In this study, we aimed to define distinct risk groups for rejection based on the combination of three molecular mismatch assessment approaches (i.e.

The gut microbiome is associated with susceptibility to febrile malaria in Malian children.

Malaria is a major public health problem, but many of the factors underlying the pathogenesis of this disease are not well understood, including protection from the development of febrile symptoms, which is observed in individuals residing in areas with moderate-to-high transmission by early adolescence. Here, we demonstrate that susceptibility to febrile malaria following Plasmodium falciparum infection is associated with the composition of the gut microbiome prior to the malaria season in 10-year-old Malian children, but not in younger children. Gnotobiotic mice colonized with the fecal samples of malaria-susceptible children were shown to have a significantly higher parasite burden following Plasmodium infection compared to gnotobiotic mice colonized with the fecal samples of malaria-resistant children.

Endophilin A2 Deficiency Impairs Antibody Production in Humans.

Endophilin A2, the sole endophilin A family member expressed in hematopoietic cells, regulates various aspects of membrane dynamics, including autophagy and endocytosis. Recent studies in rodents highlight the essential role of endophilin A2 in modulating immune responses. Here we report a homozygous frameshift variant in the SH3GL1 gene (NM_003025.

Vitamin D Receptor Gene Polymorphisms Differentiated Between Tuberculosis Disease and Infection: Causal Association Study.

Purpose: Latent tuberculosis infection (LTBI) is a critical stage in tuberculosis (TB)control, and few studies have addressed the role of vitamin D receptor(VDR) gene polymorphisms in differentiating between TB and late-onset TB from an immunogenetic perspective.

Patients And Methods: Recruitment of tuberculosis patients and latently infected population in Urumqi, Xinjiang, and use of propensity score matching(PSM) to match the two groups and control confounding to further construct a Bayesian network to analyze causal associations between VDR polymorphisms and tuberculosis disease status.

Results: 137 LTBI and 237 TB were obtained through PSM.

Disparities in Diagnosis, Access to Specialist Care and Treatment for Inborn Errors of Immunity.

Inborn errors of immunity represent a rapidly expanding group of genetic disorders of the immune system. Significant advances have been made in recent years in diagnosis, including using genetic testing and newborn screening; treatment, including precision therapies, gene therapy and hematopoietic stem cell transplant; and development of patient registries to inform prevalence, understand morbidity of these disorders and guide the development of clinical trials. However, significant disparities due to age, race, ethnicity, socioeconomic status, or geographic location exist in all aspects of care of patients with inborn errors of immunity, beginning with delays in diagnosis and further compounded by impaired access to specialist care and treatment, leading to a notable impact on outcomes including morbidity and mortality.

Epistatic effects of IGHG and FCGRIIB genes on the development of Alzheimer's disease in African Americans.

Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a large number of susceptibility genes, but most of AD heritability remains unexplained, implying the existence of additional genes. Furthermore, the majority of the GWAS have been conducted in people of European descent, and the genes important for AD susceptibility in people of African descent have been underexplored. In this hypothesis-generating prospective cohort study, we genotyped 191 African Americans (AAs) from three longitudinal cohorts on aging for the IgG3 allotype GM6, which is expressed exclusively in people of African descent, and assessed its interaction with IGHG, FCGRIIB, and HLA-DRB1 genes.

Oocyte donation pregnancies with high fetal-maternal immunogenetic dissimilarity show alterations in the maternal peripheral immunoregulatory response.

Oocyte donation (OD) pregnancies result in increased fetal-maternal immunogenetic dissimilarity due to paternal and donor-derived genes. Higher fetal-maternal HLA mismatches are correlated with preeclampsia. Therefore, this study explored the maternal immune response, focusing on regulatory T cells (Tregs) during low versus high allogeneic pregnancies, and healthy versus preeclamptic OD pregnancies.

Inflammasome-targeted therapy might prevent adverse perinatal outcomes of recurrent chronic intervillositis of unknown etiology.

Chronic histiocytic intervillositis of unknown origin (CHI) is a rare placental disorder associated with adverse pregnancy outcomes, frequent recurrence, and a lack of effective preventive strategies. Recent insights indicate a potential link between CHI-associated inflammatory lesions and the inflammasome pathway, suggesting innovative therapeutic avenues. Here we show a potential role of the inflammasome pathway in CHI through comprehensive transcriptomic analysis of grade 2 or 3 histopathologic CHI samples, paired with placental controls.

Long-term follow-up of the STOPAGO study.

In an open prospective, multicenter study enrolling 48 selected patients with chronic immune thrombocytopenia who achieved complete response for 1 year on thrombopoietin receptor agonists, half of the patients maintained a sustained response off treatment 4 years after treatment discontinuation.

SMaRT M-Seq: an optimized step-by-step protocol for M protein sequencing in monoclonal gammopathies.

In patients with monoclonal gammopathies, tumor B cells or plasma cells secrete a monoclonal antibody (M protein) that not only serves as a biomarker for tumor tracking but can also cause potentially life-threatening organ damage. This damage is driven by the patient-specific sequence of the M protein. Methods for sequencing M proteins have been limited by their high cost and time-consuming nature, and while recent approaches using next-generation sequencing or mass spectrometry offer advancements, they may require tumor cell sorting, are limited to subsets of immunoglobulin genes or patients, and/or lack extensive validation.

Autoimmune complications of tyrosine kinase inhibitors in cancer therapy: Clinical insights, mechanisms, and future perspectives.

The tyrosine kinase inhibitors (TKIs) have emerged as a promising class of novel anticancer drugs, achieving significant success in clinical applications. However, the risk of autoimmune diseases associated with these drugs has raised widespread concerns. In this review, TKI-induced autoimmune diseases are reviewed in order to understand this complex phenomenon through clinical research and molecular mechanism exploration.

Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients.

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1-14 days, 15-30 days, 31-60 days, and beyond 60 days post-transplantation.

Immunotherapeutic Potential of Mutated NPM1 for the Treatment of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one-third of adults with AML. AML NPM1 is recognized as a separate entity in the World Health Organization classification of AML.

Catching the Big Fish in Big Data: A Meta-Analysis of Zebrafish Kidney scRNA-Seq Datasets Highlights Conserved Molecular Profiles of Macrophages and Neutrophils in Vertebrates.

The innate immune system (IIS) is an ancient and essential defense mechanism that protects animals against a wide range of pathogens and diseases. Although extensively studied in mammals, our understanding of the IIS in other taxa remains limited. The zebrafish () serves as a promising model organism for investigating IIS-related processes, yet the immunogenetics of fish are not fully elucidated.