Changes in human basophil mRNA profiles during treatment with omalizumab
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ABSTRACT:
PROVIDER: PRJNA705458 | ENA |
REPOSITORIES: ENA
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Project description:Human basophils were purified from whole blood, pre-treatment (=v3) and mid-treatment (=v6) on omalizumab. In addition, basophils were isolated from non-treated, non-CSU subjects for a comparison of CSU vs. non-CSU.
2021-03-01 | GSE167882 | GEO
Project description:Patients with severe asthma may benefit from targeted biological therapies. However, personalized therapy in children and adolescents with asthma, based on individual susceptibility to molecular mechanisms addressed by different biologicals is underdeveloped. Here we established a functional in vitro model to study the differential responses of asthma patients to omalizumab (an IgE targeting biological) therapy. White blood cells isolated from asthmatic children and adolescents were pre-treated with omalizumab. Next, basophil activation and degradation were used to assess the in vitro patient’s response to omalizumab after exposure to patient-specific allergens. In parallel, basophils-specific whole RNA sequencing was used to screen for differentially expressed genes associated with in vitro response to omalizumab. The results of the screen were first confirmed in an independent cohort of patients and finally compared to the clinically relevant data. The in vitro basophil activation + degradation test may be used to study the differential response to omalizumab in patients. The differentially expressed genes in the basophils of the better vs. the poor / non-responders are predominantly associated with defense against viruses and apoptosis. The low RSAD2 expression correlates with poor response to omalizumab in vitro and with high FeNO levels (an indicator of lung inflammation) in the omalizumab-treated juvenile asthmatics. We describe an in vitro test to study the differential response to omalizumab in patients. RSAD2 may be a biomarker for response to omalizumab in asthma.
2026-02-27 | GSE281339 | 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 find genes governing basophil development or functional maturation, we analyzed the gene expression profiles of basophil progenitors by RNA-sequencing.
2023-10-31 | GSE148857 | 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 | GSE64639 | 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:To find genes regulated by Nfil3 during development or functional maturation, we analyzed the gene expression profiles of basophil progenitors by RNA-sequencing.
2023-10-31 | GSE214147 | 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: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