HLA-B*57:01+ abacavir-naive individuals have specific T cells but no patch test reactivity

摘要

Abacavir hypersensitivity (AH) is a potentially severe drag reaction that frequently involves the skin, the liver, and the lung. It is peculiar because of the following features: (a) It is strongly associated with HLA-B*57:01; 47% of HLA-B*57:1 carriers develop AH on exposure. Thus, HLA-B*57:01 has become an established marker for the identification of patients at risk of AH. (b) This strong association is not due to a hapten-like reaction to an abacavir-altered peptide but due to noncovalent binding of unmetabolized abacavir to the peptide-binding groove of HLA-B*57:01, as proposed in the p-i concept. Moreover, this abacavir binding to the HLA-B*57:01 pocket may interfere with peptide loading and cause an alteration of the presented peptide repertoire.The presentation of novel peptides may then elicit either an autoimmune reaction or an alloimmune-like reaction. (c) Abacavir-specific CD8+ T cells are detectable in the circulating blood of B*57:01+ individuals, which were never exposed to abacavir, and (d) abacavir-specific patch tests in patients with AH show high test accuracy (79%) with an excellent specificity (100%).