HLA sensitization study
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE81454 | GEO | 2016/05/17
SECONDARY ACCESSION(S): PRJNA321662
REPOSITORIES: GEO
Similar Datasets
Project description:Immune profiles were performed retrospectively in highly sensitized kidney transplant candidates Our hypothesis was that baseline differences in immune profiles could help identify candidates that respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in 20 highly sensitized kidney transplant candidates undergoing desensitization therapy.
2016-05-17 | E-GEOD-81454 | biostudies-arrayexpress
Project description:Background: We aimed to investigate the effects of intravenous immune globulin (IVIG) and rituximab desensitization treatment on kidney transplant rate and blood gene expression profiles by microrarrays. Methods: We enrolled patients with PRA levels >50% and on the deceased-donor waiting list for >5 years. Patients received IVIG (2.0 g/kg) on day 0 and 30; and rituximab (375 mg/m2) on day 15. The antibodies with mean fluorescence intensity (MFI) values > 5,000 were reported to UNET as unacceptable antigens. The gene expression profiles of blood samples collected in PAXGene tube were studied by Affymetrix HuGene 1.0 ST expression arrays. Results: 40 of the 415 patients (10%) on the waiting list were eligible for desensitization treatment and 11 completed the treatment. While 15 of the remaining 29 patients (52%) received a transplant without therapy, only 2 of the 11 desensitized patients (18%) received transplant during a median follow-up of 217 days. While there were no statistically significant difference in demographics, desensitized patients had higher cPRA values (97% vs. 77%, p=0.0005) and more number of unacceptable antigens (39 vs. 10, p=0.0001). There was no significant change in the mean number of unacceptable antigens (39 ± 22 versus 39 ± 23) or reduction in the mean MFI values (11,333 ± 3,133 vs 11,289 ± 3,386). Analysis of genes chosen as significantly differentially expressed revealed downregulation of genes involved in B cells and immune system (CD79a, B and T lymphocyte associated transcript, B cell scaffold protein, CD22, CXCR5, fas apoptotic inhibitory protein). Gene set enrichment analysis using Pathogenesis Based Transcripts created by Edmonton Group demonstrated significant downregulation of B cell associated (p=0.04) and immunoglobulin transcripts (p=0.03). Conclusion: Although, desensitization with IVIG and rituximab decreases the expression of B cell and immunoglobulin associated transcripts, it was not successful in increasing kidney transplant rate or in decreasing the number of unacceptable antigens. Total of 28 arrays included in this study, which corresponding to 9 individuals with paired pre/post treatment samples and an additional 10 untreated control individuals. pair_analysis_normData.txt for paired analysis of pre/post treatment; ordinary_analysis_normData.txt for non-paired analysis include all samples, except for 38 Pax V0 and 56 Pax V1, which shows technicial bias and lowest array quality, hence removed from analysis.
2011-08-29 | E-GEOD-31729 | biostudies-arrayexpress
Project description:Background: We aimed to investigate the effects of intravenous immune globulin (IVIG) and rituximab desensitization treatment on kidney transplant rate and blood gene expression profiles by microrarrays. Methods: We enrolled patients with PRA levels >50% and on the deceased-donor waiting list for >5 years. Patients received IVIG (2.0 g/kg) on day 0 and 30; and rituximab (375 mg/m2) on day 15. The antibodies with mean fluorescence intensity (MFI) values > 5,000 were reported to UNET as unacceptable antigens. The gene expression profiles of blood samples collected in PAXGene tube were studied by Affymetrix HuGene 1.0 ST expression arrays. Results: 40 of the 415 patients (10%) on the waiting list were eligible for desensitization treatment and 11 completed the treatment. While 15 of the remaining 29 patients (52%) received a transplant without therapy, only 2 of the 11 desensitized patients (18%) received transplant during a median follow-up of 217 days. While there were no statistically significant difference in demographics, desensitized patients had higher cPRA values (97% vs. 77%, p=0.0005) and more number of unacceptable antigens (39 vs. 10, p=0.0001). There was no significant change in the mean number of unacceptable antigens (39 ± 22 versus 39 ± 23) or reduction in the mean MFI values (11,333 ± 3,133 vs 11,289 ± 3,386). Analysis of genes chosen as significantly differentially expressed revealed downregulation of genes involved in B cells and immune system (CD79a, B and T lymphocyte associated transcript, B cell scaffold protein, CD22, CXCR5, fas apoptotic inhibitory protein). Gene set enrichment analysis using Pathogenesis Based Transcripts created by Edmonton Group demonstrated significant downregulation of B cell associated (p=0.04) and immunoglobulin transcripts (p=0.03). Conclusion: Although, desensitization with IVIG and rituximab decreases the expression of B cell and immunoglobulin associated transcripts, it was not successful in increasing kidney transplant rate or in decreasing the number of unacceptable antigens.
2011-08-30 | GSE31729 | GEO
Project description:Background: Plasmapheresis/rituximab-based desensitization therapy has successfully reduced anti-ABO antibody levels and suppressed antibody-mediated rejection (AMR) in ABO-incompatible (ABOi) kidney transplantation (KT). However, high titers of anti-ABO antibodies in some patients are refractory to standard desensitization, leading to loss of KT opportunities or AMR. Methods: Eculizumab-based desensitization was used to rescue high-titer ABOi KT patients refractory to plasmapheresis/rituximab-based desensitization. Results: The initial titers of anti-ABO IgG antibodies in the two patients were 1:512 and >1:1024; the final pre-transplant titers after desensitization were 1:128 and 1:64. Both patients received eculizumab from the day of KT to two or four weeks post-KT and maintained stable renal function up to one-year post-transplantation without overt infectious complications, despite early episodes of suspicious AMR or borderline T cell-mediated rejection. Molecular phenotype analysis of allograft biopsies using the Banff Human Organ Transplant gene panel revealed that gene expression patterns in the ABOi KT with eculizumab group overlapped with those in the ABOi KT with AMR group more than in the ABOi KT without AMR group, except for complement pathway-related gene expression. Anti-ABO antibody titers decreased to low levels 1–3 months post-transplant in the eculizumab group in parallel with decreasing anti-B-specific B cells at this time point. Conclusions: Short-term eculizumab-based desensitization therapy is promising for rescuing ABOi KT recipients with unacceptably high anti-ABO antibody titers refractory to plasmapheresis-based desensitization therapy.
2024-10-15 | GSE274052 | GEO
Project description:Diesel exhaust (DE) has been shown to enhance allergic sensitization in animals following high dose instillation or chronic inhalation exposure scenarios. The purpose of this study was to determine if short term exposures to diluted DE enhance allergic immune responses to antigen, and identify possible mechanisms using microarray technology. BALB/c mice were exposed to filtered air or diluted DE to yield particle concentrations of 500 or 2000 µg/m3 4 hr/day on days 0-4. Mice were sensitized intranasally with ovalbumin (OVA) antigen or saline on days 0-2, and 18 and all were challenged with OVA on day 28. Mice were necropsied either 4 hrs after the last DE exposure on day 4, or 18, 48, and 96 hrs after challenge. Immunological endpoints included OVA-specific serum IgE, biochemical and cellular profiles of bronchoalveolar lavage (BAL), and cytokine production in the BAL. OVA-sensitized mice exposed to both concentrations of DE had increased eosinophils, neutrophils, lymphocytes, and IL-6 post-challenge compared to OVA control, while DE/saline exposure yielded increases in neutrophils at the high dose only. Microarray analysis demonstrated distinct gene expression profiles for the high dose DE/OVA and DE/saline groups. DE/OVA induced pathways involved in oxidative stress and metabolism while DE in the absence of allergen sensitization modulated cell cycle control, growth and differentiation, G-proteins, and cell adhesion pathways. This study shows for the first time early changes in gene expression induced by the combination of diesel exhaust inhalation and antigen sensitization, which resulted in stronger development of an allergic asthma phenotype. Experiment Overall Design: Lung RNA was isolated from mice exposed to filtered air, 500 ug/m3 DE, or 2000 ug/m3 DE with or without OVA for a total of 6 exposure groups. Each group had 4 replicates for a total of 24 microarrays.
2008-06-16 | E-GEOD-9383 | biostudies-arrayexpress
Project description:Introduction. Factors contributing to kidney transplant fibrosis remain incompletely understood—particularly in the absence of acute complications. Methods. Baseline and one-year surveillance biopsies from 15 uncomplicated living donor kidney transplants were subjected to microarray and quantitative RT-PCR (qRT-PCR) analyses in order to examine changes in gene expression patterns over time. Biopsy pairs were purposefully selected from allografts with no history of acute complications and were divided into those that were histologically normal (n = 7) and those that had developed subclinical interstitial fibrosis (n = 8) at 1 year. Results. Compared to the paired baseline specimens, expression levels of 3578 probesets were found altered in all the one-year biopsies studied. A large proportion of the upregulated genes in this transplant-associated profile were functionally linked with inflammation, immunity or response to injury. These included components of inflammation-related signaling pathways (integrin, interferon and TLR) as well as individual mediators of inflammatory and immune responses. An additional 2884 probesets demonstrated altered expression in fibrotic grafts only at 1 year. The gene products in this fibrosis-associated profile were also predominantly linked with inflammation and immune function, suggesting exaggerated inflammatory activity within the fibrotic grafts. qRT-PCR analyses confirmed the predicted expression patterns for selected transcripts from the microarray profiles. Conclusions. Transcriptional profiles of histologically normal living donor renal allografts indicate that there is ongoing injury response and inflammation at 1 year compared to the immediate post-transplant period. Subclinical development of interstitial fibrosis during the first post-transplant year is associated with additional upregulation of inflammation-related genes. Keywords: time course, comparative expression We analyzed gene expression from a group of 15 renal transplant patients. All patients had histologically normal time zero biopsy but while 7 remained histologically normal (TxNorm), 8 developed subclinical interstitial fibrosis (GIF/TA) by 1 year. Patient groups were carefully selected to include patients on the same immunosuppresion therapy, transplant type, biopsy histology and absence of overt post-transplant complications (acute rejection, BK, etc). This dataset is part of the TransQST collection.
2007-03-30 | E-GEOD-7392 | biostudies-arrayexpress
Project description:We performed RNA sequencing (RNAseq) on peripheral blood mononuclear cells (PBMCs) to identify differentially expressed gene transcripts (DEGs) after kidney transplantation and after the start of immunosuppressive drugs. RNAseq is superior to microarray to determine DEGs because it’s not limited to available probes, has increased sensitivity, and detects alternative and previously unknown transcripts. DEGs were determined in adult kidney recipients, without clinical acute rejection (AR), treated with antibody induction, calcineurin inhibitor, mycophenolate, with and without steroids. Blood was obtained pre-transplant (baseline), week 1, months 3 and 6 post-transplant. PBMCs were isolated, RNA extracted and gene expression measured using RNAseq. Principal components (PCs) were computed using a surrogate variable approach. DEGs post-transplant were identified by controlling false discovery rate (FDR) at < 0.01 with at least a 2 fold change in expression from pre-transplant. The top 5 DEGs with higher levels of transcripts in blood at week 1 were TOMM40L, TMEM205, OLFM4, MMP8, and OSBPL9 compared to baseline. The top 5 DEGs with lower levels at week 1 post-transplant were IL7R, KLRC3, CD3E, CD3D, and KLRC2(Striking Image) compared to baseline. The top pathways from genes with lower levels at 1 week post-transplant compared to baseline, were T cell receptor signaling and iCOS-iCOSL signaling while the top pathways from genes with higher levels than baseline were axonal guidance signaling and LXR/RXR activation. Gene expression signatures at month 3 were similar to week 1. DEGs at 6 months post-transplant create a different gene signature than week 1 or month 3 post-transplant. RNAseq analysis identified more DEGs with lower than higher levels in blood compared to baseline at week 1 and month 3. The number of DEGs decreased with time post-transplant. Further investigations to determine the specific lymphocyte(s) responsible for differential gene expression may be important in selecting and personalizing immune suppressant drugs and may lead to targeted therapies.
2016-09-13 | GSE86884 | GEO
Project description:UNLABELLED: Achieving union between host bone and massive structural allografts can be difficult. Donor and recipient human leukocyte antigen (HLA) mismatches and recipient antibody response to donor HLA antigens might affect union. In a prospective multiinstitutional study, we enrolled a consecutive series of patients receiving cortex-replacing, massive structural bone allografts to determine the rate of donor-specific HLA antibody sensitization and to investigate the potential effect of such HLA alloantibody sensitization on allograft incorporation. HLA typing of patients and donors was determined by molecular typing methods. Donor-specific HLA sensitization occurred in 57% of the patients but had no demonstrable effect on graft incorporation or union. The type of host-allograft junction did have a major effect on graft incorporation. Cortical-to-cortical allograft-to-host junctions healed more slowly (mean, 542 days) than corticocancellous to corticocancellous allograft-to-host junctions (mean, 243 days). Although HLA sensitization does not appear to delay structural allograft bone incorporation, further followup is required to determine if there is an association between HLA sensitization and long-term graft survival. Based on these preliminary data, measures to further minimize or modulate HLA sensitization or response are not indicated at present for the purposes of improving structural bone allograft union. LEVEL OF EVIDENCE: Level II, prognostic study.
| S-EPMC2584269 | biostudies-other
Project description:In this study, investigators recruited the largest reported cohort of tolerant kidney transplant recipients who maintained their graft after ceasing to take their immunosuppression drug, and compared this cohort to subjects with stable allograft function while on immunosuppression and healthy non transplated, controls. Using gene expression studies, they identified genetic markers that are strong candidates for predicting kidney transplant candidates who may benefit from minimization or withdrawl of immunosuppression. Microarrays were used to detect expressed gene profiles of whole-blood total RNA from subjects in the tolerant, standard immunotherapy and healthy control participants
2010-06-09 | GSE22229 | GEO
Project description:Background: There is limited data on the mechanisms of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema (NIUA). Objectives: To characterize the transcriptomic and metabolomic profiles of NIUA patients undergoing aspirin desensitization. Methods: Peripheral blood mononuclear cells (PBMCs) and plasma were separated from the blood of NIUA patients undergoing aspirin desensitization for coronary artery disease and NSAID-tolerant controls. RNA was isolated from PBMCs and subjected to mRNA- and lncRNA-seq. Plasma samples were analyzed using LC-MS/MS for metabolite shifts using a semi-targeted metabolomics panel. Results: Eleven patients with NIUA and 10 healthy controls were recruited. The mRNA gene profiles of pre- versus post-desensitization and healthy control versus post-desensitization did not differ significantly. However, we identified 739 mRNAs and 888 lncRNAs as differentially expressed from pre-aspirin desensitization patients and controls. A 12-mRNA gene signature was trained using a machine learning algorithm to distinguish between controls, post-dose and pre-dose samples. Ingenuity Pathway Analysis identified 5 canonical pathways that were significantly enriched in pre-aspirin desensitization samples. Interleukin (IL)-22 was the most upregulated pathway. To investigate the potential regulatory roles of the differentially expressed lncRNA on the mRNAs, 9 lncRNAs and 12 mRNAs showed significantly correlated expression patterns in the IL-22 pathway. To validate the transcriptomics data, IL-22 was measured in the plasma samples of the subjects using ELISA. IL-22 was significantly higher in pre-aspirin desensitization patients compared to controls. In parallel, metabolomic analysis revealed stark differences in plasma profiles of pre-aspirin desensitization patients and healthy controls. In particular, 2-hydroxybenzoic acid (salicylic acid) was significantly lower in pre-aspirin desensitization patients compared to healthy controls. Conclusion: This is the first study to combine both transcriptomic and metabolomic approaches in patients with NIUA, which contributes to a deeper understanding about the pathogenesis of NIUA and may potentially pave the way towards a molecular diagnosis of NSAID hypersensitivity.
2022-12-05 | GSE219154 | GEO