Master of Science
Pathology and Laboratory Medicine
Rieder, Michael J
Delayed drug hypersensitivity reactions (DHRs) are idiosyncratic, T-cell mediated, and can present days after exposure to the culprit drug, resulting in varying degrees of skin rashes. We hypothesize that differences in activated peripheral T cell subsets and types of mediators released produce different clinical phenotypes of drug hypersensitivity reactions to sulphnamides and beta-lactam antibiotics.
We recruited participants with previous DHRs to sulfamethoxazole or beta-lactams . Peripheral blood mononuclear cells were isolated from participants. T-cell subset proliferation and activation was assessed by T-cell specific surface markers using 3H- thymidine incorporation and flow cytometry, and secreted cytokines were measured using bead-based detection.
There is insufficient evidence to conclude which T-cell subtypes are involved in different DHR clinical presentations. There were no significant differences between DHR participants and controls. More participants should be recruited to increase study power and range of clinical presentations, and consider alternate methods of identifying T-cells and modulators of interest.
Summary for Lay Audience
Delayed drug hypersensitivity reactions (DHRs) are reactions that are somehow caused by the immune system interacting with the drug. DHRs typically occur days after taking the drug, usually result in a skin rash, and are mediated by T cells. It is still unclear how the T cells cause DHRs, however there are several theories. Two commonly prescribed drugs that cause these reactions are sulfamethoxazole and beta-lactam antibiotics. We believe that reactions mediated by different types of T cells in the blood lead to the various types of skin rashes caused by DHRs.
We recruited participants who had previously visited Dr. Rieder’s drug allergy clinic and had previously tested positive for a DHR to either sulfamethoxazole or beta-lactams. We took a sample of blood from each participant, isolated a group of blood cells from the samples called “peripheral blood mononuclear cells” (PBMCs), which contains T cells. We tested these cells in different ways to see how the cells were responding to the drug. We used a technique called scintillation counting to determine if the PBMCs were growing when incubated with the drug, flow cytometry to see which type of T cell was activated in response to the drug, and Luminex to determine which molecules (cytokines) the PBMCs produced after incubation.
We have insufficient evidence to conclude which type of T cell is involved in each skin reaction. Overall, we found no differences between T cell subset activation in response to exposure to the drug treatment, while other studies have previously found differences. Changes in the methods, including increasing number of T cells used in the analysis and expanding the number of T cell subsets analyzed by flow cytometry, and increasing the cytokines analyzed by Luminex, could improve results. We only recruited eight participants, to increase the strength of the conclusions we will need to increase the number of participants. We conclude that some changes in methods could improve and produce more reliable results.
Caron, Christine, "Characterizing T Cell Phenotype In Patients With Hypersensitivity Reactions To Sulfamethoxazole And Beta-Lactam Antibiotics" (2020). Electronic Thesis and Dissertation Repository. 7278.