Role of TLR Agonist in Allergic Reactions to Drugs

Abstract

RATIONALE: Lymphocyte transformation tests (LTT) is currently the only in vitro test available for diagnosing non-immediate allergic reactions (NIR) to drugs despite its low sensitivity. Dendritic cells (DC) have been used by our group to improve LTT sensitivity although it is still not optimal with some drugs probably because DC do not achieve a complete maturation. In these cases, a concomitant stimulation by TLR similar to the one that takes place in viral infections may contribute to a complete DC maturation and therefore a higher LTT. The aim of this work was to study how the interaction of drugs and agonist with TLR of DC induce changes in DC maturation and lymphocyte proliferation. METHODS: DC maturation was analyzed by flow cytometry and T cell proliferation to the drugs by LTT in presence or absence of TLR-7/8 agonist in subjects with a confirmed maculopapular exanthema (MPE) induced either by drugs or by virus and in healthy controls. RESULTS: Data showed an increase of DC maturational markers (HLA-DR, CD80 and CD86) compared to basal conditions in patients with MPE induced by drugs or viral infection. LTT was only positive (SI > 3) to the drug responsible of the reaction and when TLR agonist was present in the culture. In healthy controls no DC maturation was observed and LTT were negative. CONCLUSIONS: The presence of virus epitopes that interact with TLR from DC may increase LTT sensitivity in the evaluation of allergic reactions to drugs that occurred concomitantly to a viral infection.