MRC CDSS & Shandong Academy of Sciences publish Dapsone Hypersensitivity Paper

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The logos of the MRC Centre for Drug Safety Science and the Shandong Academy of Sciences

Research into drug hypersensitivity associated with the expression of specific HLA alleles has focussed on the interaction between parent drug and the HLA with no attention given to reactive metabolites. For this reason, CDSS researchers have collaborated with the Shandong Institute in China to explore HLA-B*13:01-linked dapsone hypersensitivity to (a) determine whether the parent drug and/or a metabolite activates T cells and (b) determine whether HLA-B*13:01 is involved in the response.

Our study recently published in Allergy shows that dapsone and its metabolite activates CD4+ and CD8+ T-cells from hypersensitive patients via different mechanisms. Furthermore, dapsone metabolites interact with HLA-B*13:01 to activate certain CD8+ clones.

Thus, dapsone hypersensitivity should be used as an exemplar to solve the structure of drug metabolite-modified peptide HLA interactions and the relationship between HLA binding and T-cell activation.

Click here to read the paper.

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Dapsone- and nitroso dapsone-specific activation of T cells from hypersensitive patients expressing the risk allele HLA-B*13:01.

Zhao Q, Alhilali K, Alzahrani A, Almutairi M, Amjad J, Liu H, Sun Y, Sun L, Zhang H, Meng X, Gibson A, Ogese MO, Kevin Park B, Liu J, Ostrov DA, Zhang F, Naisbitt DJ.

Allergy. 2019 Mar 7. doi: 10.1111/all.13769. [Epub ahead of print]