Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Biologic agents (BA) are able to induce an adaptive immune response in a proportion of exposed patients with the onset of anti-drug antibodies (ADA), which are usually responsible for hypersensitivity reactions (HR). Drug desensitization (DD) for BA allows transient clinical tolerance to the drug in reactive patients. The paper aimed to analyse the modification of drug-specific immune responses along DD in two patients with previous ADA-mediated HR (anaphylaxis) to rituximab and tocilizumab. The in vivo and in vitro assays of humoral and cellular response to drugs were carried out in a longitudinal manner throughout the DD cycles. We observed a progressive decrease of the pre-procedure ADA titer with negativization during the DD cycles in both patients. The monitoring of the drug-specific effector cell response showed the decrease in the BA-induced proliferation, while T cell response to unrelated antigens resulted unmodified along the DD cycles. Lastly, the increase of circulating drug-specific Treg cells mainly producing IL-35 were shown during the DD treatment. This study provides evidence that DD treatment to two BA inhibits humoral and cellular anti-drug response by increasing regulatory T cells and cytokines in an antigen-restricted manner. These modifications could contribute to the safety of the procedure.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206099 | PMC |
| http://dx.doi.org/10.1038/s41598-021-91851-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights into regulatory T-cell and type-I interferon roles in determining abacavir-induced hypersensitivity or immune tolerance.
Front Immunol
June 2025
Division of Pharmaceutical Quality Research IV, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.
Introduction: Clinical use of several small molecule drugs may lead to severe T-cell-mediated idiosyncratic drug hypersensitivity reactions (iDHR) linked to HLA alleles, including abacavir (ABC) with HLA-B*57:01. Due to study limitations in humans, pathogenic networks in iDHR remain elusive. HLA transgenic murine models have been proposed to bridge knowledge gaps in tolerance and susceptibility to drugs.
View Article and Find Full Text PDFFeedback regulation of VISTA and Treg by TNF-α controls T cell responses in drug allergy.
Allergy
May 2025
Hospital for Skin Diseases, Shandong First Medical University, Jinan, Shandong, China.
Background: Severe cutaneous adverse reactions (SCARs) mediated by cytotoxic T lymphocytes are a series of life-threatening conditions with a mortality of 4%-20%. The clinical application of tumor necrosis factor-alpha (TNF-α) antagonist improves the outcome of some SCARs patients; however, this is complicated by the elusive and varied immunopathogenesis.
Methods: To clarify the precise process and optimize the therapy regimen of SCARs, we performed single-cell sequencing, in vitro functional and clinical analysis of patients with SCARs.
Transgenic murine models for the study of drug hypersensitivity reactions linked to HLA-I molecules.
Curr Opin Allergy Clin Immunol
August 2023
Laboratory of Immunology, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration. Silver Spring, Maryland 20993, USA.
Purpose Of Review: Immune-mediated drug hypersensitivity reactions (DHRs) can be life-threatening and an impediment to drug development. Mechanism of disease studies are difficult to perform in humans. Here we review human leukocyte antigens class I (HLA-I) transgenic murine models and highlight how these systems have helped to elucidate drug-specific and host immune factors that initiate, propagate and control severe drug toxicities to skin and liver.
View Article and Find Full Text PDFDevelopment and initial validation of a modified lymphocyte transformation test (LTT) assay in patients with DRESS and AGEP.
Allergy Asthma Clin Immunol
October 2022
Department of Clinical Immunology and Allergy, Royal North Shore Hospital, Sydney, NSW, Australia.
Background: The lymphocyte transformation test (LTT) is an in vitro assay used to diagnose drug induced hypersensitivity reactions by detecting the activation and expansion of drug-specific memory T cells to the suspected implicated drug. Traditionally radiolabelled thymidine (3H-thymidine) has been used but requires the handling and disposal of radioactive materials.
Objective: To examine safe alternatives to 3H-thymidine, test assay modifications for improved assay sensitivity and evaluate the modified LTT in patients with DRESS and AGEP.
Cyclosporine A but Not Corticosteroids Support Efficacy of Expanded, Adoptively Transferred Human Tregs in GvHD.
Front Immunol
December 2021
Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH-Center for Regenerative Therapies (BCRT), Berlin, Germany.
Reshaping the immune balance by adoptive transfer of regulatory T-cells (Tregs) has emerged as a promising strategy to combat undesired immune reactions, including in Graft-versus-Host Disease (GvHD), which is the most lethal non-relapse complication of allogeneic hematopoietic stem cell transplantation. Currently however, little is known about the potentially inhibitory effects of conventional immunosuppressive drugs, which are routinely used to treat GvHD, on adoptively transferred Tregs. Here we demonstrate drug-specific effects of the conventional immunosuppressive drugs Cyclosporine A, Mycophenolate mofetil and methylprednisolone on adoptively transferred Tregs in a humanized NOD/SCID/IL2Rgamma-/- GvHD mouse model.
View Article and Find Full Text PDF