RT Journal Article
T1 Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis: the influence of human leucocyte antigen alleles.
A1 Stephens, Camilla
A1 Castiella, Agustin
A1 Gomez-Moreno, Eva M
A1 Otazua, Pedro
A1 López-Nevot, Miguel Ángel
A1 Zapata, Eva
A1 Ortega-Alonso, Aida
A1 Ruiz-Cabello, Francisco
A1 Medina-Cáliz, Inmaculada
A1 Robles-Díaz, María Mercedes
A1 Soriano, German
A1 Roman, Eva
A1 Hallal, Hacibe
A1 Moreno-Planas, José M
A1 Prieto, Martin
A1 Andrade-Bellido, Raúl Jesús
A1 Lucena-González, María Isabel
K1 Hepatotoxicidad
K1 Hígado - Enfermedades
K1 Farmacogenética
K1 Sistema inmunológico
K1 Complejo mayor de histocompatibilidad
AB Objectives: Positive autoantibody (AAB) titres are commonly encountered inautoimmune 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 toanalyse 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 885healthy Spanish controls.Results: Compared with controls, HLA-B*08:01 [44 vs. 9.7%, P = 3.7E − 13/correctedP-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*01:01frequency was increased in the same population, but did not reach significance afterBonferroni’s correction (34 vs. 19%, P = 0.02/Pc = 0.37). Fifty-eight of 207 DILI patientspresented positive titres for at least one AAB (predominantly antinuclear antibody 76%and antismooth muscle antibody 28%). There was a tendency towards higherrepresentation of DRB1*14:01 and DQB1*05:03 in DILI AAB + compared with DILIAAB − (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, DQB1*02:01and possibly A*01:01 enhances the risk of AIH (type 1) in Spanish patients. These allelesform part of the ancestral haplotype 8.1. HLA-DRB1*14:01 and DQB1*05:03 couldpotentially increase the risk of positive AAB (particularly antinuclear antibody) inSpanish DILI patients. Pharmacogenetics and Genomics.
PB Lippincott Williams & Wilkins
YR 2016
FD 2016-09
LK https://hdl.handle.net/10630/40274
UL https://hdl.handle.net/10630/40274
LA eng
NO Camilla Stephens, Agustin Castiella, Eva M Gomez-Moreno, Pedro Otazua, Miguel-Ángel López-Nevot, Eva Zapata, Aida Ortega-Alonso, Francisco Ruiz-Cabello, Inmaculada Medina-Cáliz, Mercedes Robles-Díaz, German Soriano, Eva Roman, Hacibe Hallal, José M Moreno-Planas, Martin Prieto, Raúl J Andrade, M Isabel Lucena. Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis: the influence of human leucocyte antigen alleles. Pharmacogenet Genomics 2016 Sep;26(9):414-422
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 22 ene 2026