The Low Expression of Tim-3 in Patients with Maculopapular Exanthema (EMP) Induced By Drugs Can Impaired Disease Control.

Rationale: In cutaneous non-immediate reactions to drugs, like EMP, several lymphocyte subtypes are involved, mainly with a Th1-phenotype. However the involvement of other lymphocyte subtypes like Th17-cells has not been studied yet. Moreover, numbers of both lymphocyte subsets can be controlled by the interaction of the receptor Tim3 with Gal9 inducing their apoptosis. The aim of the study was to analyse the expression of Tim3 in patients with drug induced EMP.

Methods: Peripheral blood cells (PBMC) and skin biopsies were obtained from 18 allergic patients and 10 tolerant subjects. Immunohistochemical staining and flow cytometry were carried out to determine the presence of Th1 (CXCR3⁺) and Th17 (RORgt⁺IL17⁺) CD4-cells and the expression of Tim3. 

Results: The involvement of Th1-CD4-cells in EMP were confirmed, with higher levels compared to controls in both, skin (p<0.0001) and PBMC (p=0.032 during the acute phase and p=0.039 after resolution). However, we could not find any difference in the frequencies of Th17-cells between patients and controls. The expression of Tim3, was strongly decreased in patients (p<0.0001 in skin), mainly in Th1-CD4-cells during the acute phase (p<0.0001), but also after resolution (p=0.039). Interestingly, the expression of Tim3 in Th17-cells was similar in patients and controls.

Conclusions: The low expression of Tim3 in the effector cells during the acute phase could be the responsible of the impaired regulation of these cells in EMP. Their low expression after resolution could serve as a biomarker for these reactions. This axis could be a target to develop strategies to control and diagnose these reactions.