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Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis: the influence of human leucocyte antigen alleles

Stephens, Camilla, Castiella, Agustin, Gomez-Moreno, Eva M., Otazua, Pedro, López-Nevot, Miguel-Ángel, Zapata, Eva, Ortega-Alonso, Aida, Ruiz-Cabello, Francisco, Medina-Cáliz, Inmaculada, Robles-Díaz, Mercedes, Soriano, German, Roman, Eva, Hallal, Hacibe, Moreno-Planas, José M., Prieto, Martin, Andrade, Raúl J., Lucena, M. Isabel·2016·Pharmacogenetics and Genomics
DOI 10.1097/fpc.0000000000000230
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Abstract

Objectives Positive autoantibody (AAB) titres are commonly encountered in autoimmune hepatitis (AIH) and in a proportion of drug-induced liver injury (DILI) patients. The underlying mechanism for selective AAB occurrence in DILI is unknown, but could be associated with variations in immune-associated genes. Hence, we aimed to analyse human leucocyte antigen (HLA) allele compositions in DILI with positive (+) and negative (-) AAB titres and in AIH patients. Methods High-resolution genotyping of HLA class I (A, B, C) and II (DRB1, DQB1) loci was performed on 207 DILI and 50 idiopathic AIH patients and compared with 885 healthy Spanish controls. Results Compared with controls, HLA-B*08:01 [44 vs. 9.7%, P=3.7E-13/corrected P-value (Pc)=1.0E-11], C*07:01 (46 vs. 24%, P=6.4E-04/Pc=0.012), DRB1*03:01 (58 vs. 21.5%, P=5.0E-09/Pc=1.0E-07) and DQB1*02:01 (56 vs. 22%, P=6.8E-08/Pc=9.0E-07) were significantly more frequent in AIH patients. The HLA-A*01:01 frequency was increased in the same population, but did not reach significance after Bonferroni's correction (34 vs. 19%, P=0.02/Pc=0.37). Fifty-eight of 207 DILI patients presented positive titres for at least one AAB (predominantly antinuclear antibody 76% and antismooth muscle antibody 28%). There was a tendency towards higher representation of DRB1*14:01 and DQB1*05:03 in DILI AAB+ compared with DILI AAB- (13.8 vs. 4.0%, P=0.02/Pc=0.5; 13.8 vs. 4.7%, P=0.04/Pc=0.5). Conclusion The presence of HLA alleles B*08:01, C*07:01, DRB1*03:01…

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Metadata

Authors
Stephens, C., Castiella, A., Gomez-Moreno, E. M., Otazua, P., López-Nevot, M.-Á., Zapata, E., Ortega-Alonso, A., Ruiz-Cabello, F., Medina-Cáliz, I., Robles-Díaz, M., Soriano, G., Roman, E., Hallal, H., Moreno-Planas, J. M., Prieto, M., Andrade, R. J., & Lucena, M. I.
Venue
Pharmacogenetics and Genomics
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-09
Volume
26
Issue
9
Pages
414-422
ISSN
1744-6872
DOI
10.1097/fpc.0000000000000230
Cited by
22
References
1
Language
en

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