HLA-B57:01+ abacavir-naive individuals have specific T cells but no patch test reactivity

[...]HLA-B*57:01 has become an established marker for the identification of patients at risk of AH.1 (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*57:01,2...

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Published inJournal of allergy and clinical immunology Vol. 132; no. 3; pp. 756 - 758
Main Authors Schnyder, Benno, MD, Adam, Jacqueline, PhD, Rauch, Andri, MD, Thurnheer, Maria C., MD, Pichler, Werner J., MD
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.09.2013
Elsevier Limited
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Summary:[...]HLA-B*57:01 has become an established marker for the identification of patients at risk of AH.1 (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*57:01,2-5 as proposed in the p-i concept.6 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.2-4 The presentation of novel peptides may then elicit either an autoimmune reaction or an alloimmune-like reaction.2-4 (c) Abacavir-specific CD8+ T cells are detectable in the circulating blood of B*57:01+ individuals, which were never exposed to abacavir,5,7 and (d) abacavir-specific patch tests in patients with AH show high test accuracy (79%) with an excellent specificity (100%).1 On the basis of these peculiarities and findings, we performed a study (approved by the Ethics Committee of the canton of Bern, Switzerland) in which we asked the following questions: [...]while all HLA-B*57:01+ individuals have abacavir-reactive T cells in the circulation, skin testing in abacavir-naive individuals is negative and does not appear to sensitize.
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ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2013.04.013