Polymorphism and immunosuppression

Asporin (ASPN) has been identified as one of the members of the class I small leucine-rich proteoglycans (SLRPs) family in the extracellular matrix (ECM). It is involved in classic ensigns of cancers such as self-dependent growth, resistance to growth inhibitors, restricting apoptosis, cancer metastasis, and bone-related disorders. ASPN is different from other members of SLRPs, such as decorin (DCN) and biglycan (BGN), in a way that it contains a distinctive length of aspartate (D) residues in the amino (N) -terminal region...

Tacrolimus is the principal immunosuppressive drug which is administered after heart transplantation. Managing tacrolimus therapy is challenging due to a narrow therapeutic index and wide pharmacokinetic (PK) variability. We aimed to establish a physiologically based pharmacokinetic (PBPK) model of tacrolimus in adult heart transplant recipients to optimize dose regimens in clinical practice. A 15-compartment full-PBPK model (Simbiology® Simulator, version 5.8.2) was developed using clinical observations from 115 heart transplant recipients...

Transforming growth factor-β1 (TGF-β1), a cytokine with immunosuppressive and pro-fibrogenic activity, is a potential marker of infection, liver transplant rejection, and fibrosis. Its levels in the blood and tissues depend on many factors; however, the role of gene polymorphism is still unclear. In this work, the distribution frequency of three single nucleotide polymorphism (SNP) variants of the Tgfb1 gene, namely rs1800469, rs1800470, and rs1800471, was studied in children with end-stage liver disease (ESLD)...

BACKGROUND: Many factors affect the survival rate after kidney transplantation, including laboratory tests, medicine therapy and pharmacogenomics. Tacrolimus, mycophenolate mofetil and methylprednisolone were used as an immunosuppressive regimen after kidney transplantation. The primary goal of this study was to investigate the factors affecting the tacrolimus concentrations and mycophenolate mofetil area under the curve of mycophenolic acid AUC-MPA. Secondary goals were to study the association between perioperative period laboratory tests, medicine therapy, CYP3A5 genetic polymorphisms, and survival rate in kidney renal transplant patients...

Monoclonal antibodies (mAbs) are an important treatment option for COVID-19 caused by SARS-CoV-2, especially in immunosuppressed patients. However, this treatment option can become ineffective due to mutations in the SARS-CoV-2 genome, mainly in the receptor binding domain (RBD) of the spike (S) protein. In the present study, 7950 SARS-CoV-2 positive samples from the Uppsala and Örebro regions of central Sweden, collected between March 2022 and May 2023, were whole-genome sequenced using amplicon-based sequencing methods on Oxford Nanopore GridION, Illumina MiSeq, Illumina HiSeq, or MGI DNBSEQ-G400 instruments...

Livedoid vasculopathy (LV) is a chronic coagulation disorder characterized by recurrent, painful ulcers on the lower extremities. Methylene tetrahydrofolate reductase ( MTHFR ) gene polymorphism is associated with coagulopathy. Therapeutic options usually include anti-inflammatory or immunosuppressive agents. However, the condition is still highly challenging to manage and no consensus over the first-line treatment for LV exists. Furthermore, when LV is accompanied with MTHFR gene polymorphism, clinical presentations could be more severe and resistant to treatment...

Mannose-binding lectin 2 (MBL2), a member of the multimeric lectin family, is crucial in immune regulation and tumor development. MBL2 gene polymorphisms are associated with the risk and prognosis of various tumors, including hepatocellular carcinoma (HCC). Its functional role in HCC remains largely unclear. In this study, we aimed to identify whether MBL2 is a key regulator and a potential therapeutic target for HCC. A bioinformatics analysis revealed close relationships among MBL2 downregulation, the tumor-associated proliferation and metastasis pathway, and tumor immunosuppressive microenvironments...

PURPOSE: We aimed to investigate the association between ATP Binding Cassette Subfamily B Member 1 (ABCB1) single nucleotide polymorphisms (SNPs) and the pharmacokinetics of tacrolimus. METHODS: A systematic search was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase from inception to November 2022. Outcomes included weight-adjusted daily dose (DD) and dose-adjusted trough concentration (C0/Dose). RESULTS: A total of 1059 liver or kidney transplant recipients from 14 publications were included...

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are polymorphic, adherent cells with the capability to stimulate tissue regeneration and modulate immunity. MSCs have been broadly investigated for potential therapeutic applications, particularly immunomodulatory properties, wound healing and tissue regeneration. The exact physiologic role of MSCs, however, remains poorly understood, and this gap in knowledge significantly impedes the rational development of therapeutic cells. Here, we considered interferon γ (IFN-γ) and tumor necrosis factor alpha (TNF-α), two cytokines likely encountered physiologically and commonly used in cell manufacturing...

INTRODUCTION: Bullous pemphigoid (BP) is considered the most common bullous autoimmune disorder, characterized by autoantibodies directed against hemidesmosomes in the skin and mucous membranes. It usually affects elderly individuals in the sixth through eighth decades of life, with an average age at onset of 65 years. Only a few cases have been reported in children and teenagers. CASE PRESENTATION: Herein, we report a 17-year-old boy who presented with a pruritic vesicular rash on his arms and legs accompanied by erythema...

BACKGROUND: Tacrolimus (TAC) is the mainstay of immunosuppressive regimen for kidney transplantations. Its clinical use is complex due to high inter-individual variations which can be partially attributed to genetic variations at the metabolizing enzymes CYP3A4 and CYP3A5. Two single nucleotide polymorphisms (SNPs), CYP3A4*22 and CYP3A5*3, have been reported as important causes of differences in pharmacokinetics that can affect efficacy and/or toxicity of TAC. OBJECTIVE: Investigating the effect of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration in Egyptian renal recipients...

Solid organ transplant donor-recipient eplet mismatch has been correlated with donor-specific antibody (DSA) formation, antibody-mediated rejection, and overall rejection rates. However, studies have been predominantly in patients on tacrolimus-based immunosuppression regimens and have not fully explored differences in ethnically and racially diverse populations. Evidence indicates that patients on belatacept have lower rates of DSA formation, suggesting mediation of the immunogenicity of mismatched human leukocyte antigen polymorphisms...

Although polymorphic microbiomes have emerged as hallmarks of cancer, far less is known about the role of the intratumor mycobiome as living microorganisms in cancer progression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomic sequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancer mice models, we find that A. sydowii promotes lung tumor progression via IL-1β-mediated expansion and activation of MDSCs, resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulation of PD-1+ CD8+ T cells...

Human Natural Killer (NK) cells are heterogeneous lymphocytes regulated by variegated arrays of germline-encoded activating and inhibitory receptors. They acquire the ability to detect polymorphic self-antigen via NKG2A/HLA-E or KIR/HLA-I ligand interactions through an education process. Correlations among HLA/KIR genes, kidney transplantation pathology and outcomes suggest that NK cells participate in allograft injury, but mechanisms linking NK HLA/KIR education to antibody-independent pathological functions remain unclear...

Paraneoplastic pemphigus (PNP) is a rare, autoimmune, blistering condition defined by severe stomatitis, polymorphous cutaneous eruptions, and underlying neoplasms. PNP associated with solid cancer is extremely rare. An association with prostate adenocarcinoma remains exceptional. We describe a 69-year-old patient with recalcitrant PNP associated with prostate adenocarcinoma showing spectacular response immediately after associating hormonotherapy with conventional immunosuppressive drugs.

Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is undefined. We investigated the clinical consequences of a genetic predisposition toward lower WBC counts among 89,559 biobank participants from tertiary care centers using a polygenic score for WBC count (PGS WBC ) comprising single nucleotide polymorphisms not associated with disease. A predisposition to lower WBC counts was associated with a decreased risk of identifying pathology on a bone marrow biopsy performed for a low WBC count (odds-ratio=0...

Tacrolimus is an immunosuppressant with a narrow therapeutic index and pharmacokinetic variability. This variability may be attributed to genetic variants in gene CYP3A5 associated with Tacrolimus metabolism. Studies focusing on genetic variants in the CYP3A5 gene associated with Tacrolimus metabolism have been published, a meta-analysis of these published articles may provide a direction that can change the future research and clinical management of renal transplant patients. In this systematic review and meta-analysis, we have reviewed and analyzed the studies and clinical trials conducted to determine the association between genetic variants of CYP3A5 and Tacrolimus metabolism from the PubMed database and clinical trials (www...

Tacrolimus (TAC) is a narrow-therapeutic-range immunosuppressant drug used after organ transplantation. A therapeutic failure is possible if drug levels are not within the therapeutic range after the first year of treatment. Pharmacogenetic variants and drug-drug interactions (DDIs) are involved. We describe a patient case of a young man (16 years old) with a renal transplant receiving therapy including TAC, mycophenolic acid (MFA), prednisone and omeprazole for prophylaxis of gastric and duodenal ulceration...

Purpose: Tacrolimus (Tac) is a widely used immunosuppressive agent in kidney transplantation. Cytochrome P450 (CYP), especially CYP3A4 enzymes are responsible for the metabolism of drugs. However, the correlation between plasma Tac concentration and CYP3A4*22 gene variants is controversial. This meta-analysis aims to evaluate the association between CYP3A4*22 polymorphism and the dose-adjusted trough concentration (C0 /D) of Tac in adult kidney transplant patients. Methods: We conducted a literature review for qualifying studies using the PubMed, Web of Science, and Embase databases until July 2023...

CONTEXT: Idiopathic membranous nephropathy (IMN) is a common pathologic type of nephrotic syndrome, and the level of the M-type phospholipase A2 receptor (PLA2R) antibody can serve as one index for predicting its progression and prognosis. However, patients with the same level can show great differences in their responses and prognoses. OBJECTIVES: The study aimed to explore the relationship between a PLA2R gene polymorphism combined with an immunoglobulin G (IgG) subclass in renal tissues and patients' responses to immunosuppressive therapy, to determine the clinical prognosis for IMN patients...