Changes in human basophil mRNA profiles during treatment with omalizumab
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE167882 | GEO | 2021/03/01
REPOSITORIES: GEO
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Project description:Background: Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterised by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineage-CD34hiCD117int/hiFcεRI+ cells in blood have previously been shown to represent a mast cell precursor. Methods: We enumerated FcεRI-, FcεRI+ and FcεRIhi lineage-CD34+CD117+ cells using flow cytometry in blood of patients with CSU (n=55), including 12 patients receiving omalizumab and 43 not receiving omalizumab (n=43). Twenty-two control samples were studied. Disease control and patient response to omalizumab was evaluated using the Urticaria Control Test. We performed single cell RNA sequencing (scRNA-seq) on lineage-CD34hiCD117hi blood cells from a subset of patients with CSU (n=8) and healthy controls (n=4). Results: CSU patients had more Lineage-CD34+CD117+FcεRI+ blood cells than controls. Lineage-CD34+CD117+FcεRI+ cells were significantly higher in patients with CSU who had an objective clinical response to omalizumab when compared to patients who had poor disease control 90 days after initiation of omalizumab. scRNA-seq revealed that lineage-CD34+CD117+FcεRI+ cells contained both lymphoid and myeloid progenitor lineages, with omalizumab responsive patients having proportionally more myeloid progenitors. The myeloid progenitor lineage contained small numbers of true mast cell precursors along with more immature FcεRI- and FcεRI+ myeloid progenitors. Conclusion: Increased blood CD34+CD117+FcεRI+ cells may reflect enhanced bone marrow egress in the setting of CSU. High expression of these cells strongly predicts better clinical responses to the anti-IgE therapy, omalizumab.
2024-04-30 | GSE261424 | GEO
Project description:A considerable proportion of patients with H1-antihistamine-resistant chronic spontaneous urticaria (CSU) fails to respond to omalizumab. However, there is yet no available biomarker that accurately predicts such a response outcome. The utility of blood basophil and eosinophil levels and exosomal and basophil micro(mi)RNAs as biomarkers of response to omalizumab in CSU was explored. In this prospective cohort study of twenty patients with antihistamine-resistant CSU, subjects were treated with 3-monthly doses of omalizumab, and their response assessed using the weekly urticaria activity score (UAS7) for a period of 12-weeks. Basophil and eosinophil levels in the blood and differentially expressed exosomal and basophil miRNAs of complete responders compared to non-responders were identified at baseline. Canonical pathways, altered by differentially expressed miRNAs, were identified using Ingenuity Pathway Analysis (IPA). Complete responders had higher baseline basophil levels (≥21 cells/L) in the peripheral blood compared to non-responders (P = 0.005). Baseline levels of eosinophils did not differ between the study groups. Complete responders in comparison to non-responders had an expression profile characterized by a significantly higher expression of six exosomal miRNAs (miR-6499-5p, miR-7848, miR-4494-3p, miR-450a-2-3p, miR-6877-3p, and miR-3976) and lower expression of miR-141-3p. Complete responders also had higher expression of three basophil miRNAs (miR-1200, miR-1236-3p, and miR-4496). The exosomal miRNA expression profile was predicted by IPA to alter Tec Kinase Signaling pathway activity (P = 0.003).
2021-11-16 | GSE153579 | GEO
Project description:To investigate blood transcriptional changes induced by omalizumab treatment and to determine variations between omalizumab responders and non-responders.
2020-07-19 | GSE134544 | GEO
Project description:Background : Biologic therapies have transformed severe asthma management, particularly for T2-high asthma. We aimed to investigate blood proteomics and transcriptomics after biologic treatment. Methods : A prospective study was conducted on 35 patients with severe T2-high asthma treated with mepolizumab (n=9), benralizumab (n=14), or omalizumab (n=12). Evaluations occurred at baseline and after 16 weeks (omalizumab) or 24 weeks (mepolizumab, benralizumab) of treatment. Blood samples were collected. Gene expression was analyzed via Illumina TruSeq RNA Prep, with RNA sequencing on the Illumina NovaSeq-6000 platform. Results : RNA-seq analysis revealed 86 down-regulated genes common to both mepolizumab and benralizumab, primarily associated with eosinophils, basophils, and the purinergic receptor signaling pathway. Additionally, there was evidence of gene regulation involved in antiviral immunity. However, specific gene modulation was observed for benralizumab (114 genes) and mepolizumab (68 genes). Changes following omalizumab treatment were minimal, with only three significantly down-regulated genes. Conclusion : While omalizumab showed minimal quantifiable effects on gene expression, mepolizumab and benralizumab—despite exhibiting distinct profiles—both induced down-regulation of genes related to eosinophil and basophil biology and purinergic signaling pathways, alongside up-regulation of genes involved in innate antiviral immunity.
2025-12-13 | GSE298740 | GEO
Project description:In this study, we explored gene expression profiles of CD34-CLEC12Ahi pre-basophils isolated from the bone marrow as well as CD34-CLEC12Alo mature basophils from the bone marrow and CD34+ basophil progenitors. We revealed that the gene expression of mature basophils isolated from the bone marrow and spleen resembled each other whereas pre-basophils and mature basophils showed distinct gene expression profiles.
2023-03-21 | GSE206591 | GEO
Project description:Changes in human basophil mRNA profiles during treatment with omalizumab
| PRJNA705458 | ENA
Project description:Human basophils were examined in vitro for changes in their mRNA expression profiles during stimulation under a variety of conditions. Basophils were obtained from two sources prior to purification, residual cell packs from leukapheresis procedures (which represent the 80% of the sample results) or by venipuncture. For cells obtained by leukapheress, purification included application of elutration, 2-step Percoll gradients and negative selection on Miltenyi columns using StemSep basophil isolation antibodies (see J. Immunol. Methods, 385:51, 2012). For cells obtained by venipuncture, purification included application of 2-step Percoll gradients following by negative selection on Miltenyi columns using StemSep basophil isolation antibodies. The time from subject donation to the start of an in vitro study (first lysis for mRNA) ranged from 6-7 hours for leukapheresis packs to 4-5 hours for venipuncture. Basophil purities averaged 99% for these studies. For most of the studies, purified basophils were incubated in RPMI-1640 media supplemented with human serum albumin (0.03%), 20 µg/ml gentamycin and glutamine (as glutamax) for several hours to 3 days depending on the stimulus. For most experiments, the day 0 lysis acted as the initial control in order to examine profiles for changes due to simple culture. The study included stimulation with interleukin-3, inteleukin-33, interleukin-5, interleukin-2, nerve growth factor, anti-IgE antibody (6061P, Hybridoma Labs, Maryland) or fmet-leu-phe (FMLP) and the sample title indicates the mode and length of stimulation.
2015-03-20 | GSE64639 | GEO
Project description:It has been previously shown that airway exposure to Toll-like receptor ligands through lipopolysaccharide (LPS)-contaminated house dust or bacterial infections can exacerbate allergic inflammation; however, the underlying mechanism(s) controlling this response have not been fully elucidated. Here we report that basophils are the major source of Th2 cytokines that respond to TLR4 ligands, such as LPS and lipid A, in human PBMC and murine spleen cells. LPS activated human PBMCs to up-regulate mRNAs for not only pro-inflammatory cytokines such as IL-6 and chemokines such as CXCL8 (IL-8), CCL2 (MCP-1), but also Th2 cytokines such as IL-4 and IL13. Among PBMCs, we identified CD123+/BDCA4- basophils as the major source of IL-4 and IL-13 in response to LPS. Even in the absence of IgE, purified human basophils, as well as a basophilic cell line, were directly activated by LPS to produce IL-4 and IL-13. Moreover, LPS-stimulated IL-4 knockin mouse (4get mice) spleens identified the basophils as the major IL-4 producing cells in a TLR4-dependent manner. These results indicate that bacterial LPS may play a role in type-2 immunity through direct activation of basophils to produce IL-4 and IL-13. Keywords: Cell type comparison
2013-12-31 | GSE8589 | GEO
Project description:Human basophils were examined in vitro for changes in their mRNA expression profiles during stimulation under a variety of conditions. Basophils were obtained from two sources prior to purification, residual cell packs from leukapheresis procedures (which represent the 80% of the sample results) or by venipuncture. For cells obtained by leukapheress, purification included application of elutration, 2-step Percoll gradients and negative selection on Miltenyi columns using StemSep basophil isolation antibodies (see J. Immunol. Methods, 385:51, 2012). For cells obtained by venipuncture, purification included application of 2-step Percoll gradients following by negative selection on Miltenyi columns using StemSep basophil isolation antibodies. The time from subject donation to the start of an in vitro study (first lysis for mRNA) ranged from 6-7 hours for leukapheresis packs to 4-5 hours for venipuncture. Basophil purities averaged 99% for these studies. For most of the studies, purified basophils were incubated in RPMI-1640 media supplemented with human serum albumin (0.03%), 20 µg/ml gentamycin and glutamine (as glutamax) for several hours to 3 days depending on the stimulus. For most experiments, the day 0 lysis acted as the initial control in order to examine profiles for changes due to simple culture. The study included stimulation with interleukin-3, inteleukin-33, interleukin-5, interleukin-2, nerve growth factor, anti-IgE antibody (6061P, Hybridoma Labs, Maryland) or fmet-leu-phe (FMLP) and the sample title indicates the mode and length of stimulation.
2015-03-20 | GSE64638 | GEO
Project description:E-cadherin is a key regulator of epithelial cell-cell adhesion, which loss accelerates tumor growth and invasion. Aside epithelia, E-cadherin is also expressed in hematopoietic cells. The function of hematopoietic E-cadherin is however mostly elusive. In this study, we validated mouse models for functional investigation of hematopoietic E-cadherin in human hematopoiesis. We generated a hematopoietic specific E-cadherin knockout mouse model. In mice, hematopoietic E-cadherin is predominantly expressed within the basophil lineage, which expression is dispensable for the generation of basophils. Remarkably, E-cadherin mRNA or protein were not detected in human basophils. In contrast, human hematopoietic E-cadherin marks the erythroid lineage. E-cadherin expression in hematopoiesis thereby revealed striking evolutionary differences within the basophil and erythroid cell lineage between human and mouse. This is remarkable as E-cadherin expression in epithelia is highly conserved among vertebrates including human and mouse. Our study therefore revealed that the mouse does not represent a suitable model to study the function of E-cadherin in human hematopoiesis. Mouse models can be used to define the role of E-cadherin in basophils, which regulation however may not be conserved in human basophils. Overall, our study underscores the need to develop alternative means to study the role of E-cadherin in human erythropoiesis.
2022-11-15 | GSE211102 | GEO