title: Flow cytometry test to screen for HLA-B*58:01-associated allopurinol hypersensitivity.
abstract: A strong association between the human leucocyte antigen (HLA)-B*58:01 allele and allopurinol-associated severe cutaneous adverse reactions (SCAR) has been reported. A screening for HLA-B*58:01 before allopurinol has been suggested in guidelines for management of gout. HLA-B*58:01 screening is generally based on molecular biology methods that may be not suitable for wide application. We have retrospectively evaluated the performance on a rapid flow cytometry (FCM) test, based on the use of a monoclonal antibody specific for HLA-B17, an antigen that can be split into HLA-B*57 and -B*58 alleles by molecular biology testing, which is used to screen for HLA-B*57:01 before prescription of the antiretroviral agent abacavir in HIV-positive patients. Among 475 samples that were analysed by FCM and by molecular biology test as gold standard, 2 out of 89 false negative tests for HLA-B*58:01 were found. The sensitivity was 97.8% and the negative predictive value was 98.9%. We have shown that a FCM test can identify almost all HLA-B*58:01 positive individuals. As FCM laboratories are more widely available than molecular biology ones, this approach could be used to reduce the risk for allopurinol-induced SCAR. Where both facilities are available, a two-step strategy (FCM as screening, molecular biology for confirmation) may reduce the cost of the screening.
authors.affiliation: Rheumatology and Clinical Immunology Unit, Spedali Civili and University of Brescia, piazzale Spedali Civili, 1, 25123, Brescia, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Scarsi
authors.forename: Carla
authors.initials: C
authors.lastname: Bosio
authors.forename: Silvia
authors.initials: S
authors.lastname: Coccoli
authors.forename: Amilcare
authors.initials: A
authors.lastname: Barucco
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tavelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Airò
mesh_terms: D000483:Alleles; D000493:Allopurinol / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015224:Dideoxynucleosides / Q000737:chemistry; D004342:Drug Hypersensitivity / Q000097:blood*; D005188:False Negative Reactions; D005434:Flow Cytometry / Q000379:methods*; D015235:HLA-B Antigens / Q000097:blood*; D006801:Humans; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012871:Skin Diseases / Q000097:blood; D000099227:Abacavir
chemical_list: D000493:Allopurinol; D000911:Antibodies, Monoclonal; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D000099227:Abacavir; C500126:HLA-B*58:01 antigen
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