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Genetic association between CD96 locus and immunogenicity to anti-TNF therapy in Crohn's disease.
The Pharmacogenomics Journal ( IF 2.9 ) Pub Date : 2019-05-02 , DOI: 10.1038/s41397-019-0090-4 Adrià Aterido 1, 2 , Núria Palau 1 , Eugeni Domènech 3, 4 , Pilar Nos Mateu 4, 5 , Ana Gutiérrez 4, 6 , Fernando Gomollón 4, 7 , Juan L Mendoza 8 , Esther Garcia-Planella 9 , Manuel Barreiro-de Acosta 10 , Fernando Muñoz 11 , Maribel Vera 12 , Cristina Saro 13 , Maria Esteve 4, 14 , Montserrat Andreu 15 , María Chaparro 4, 16 , Julián Panés 4, 17 , Valle García-Sánchez 18 , María López-Lasanta 1 , Andrea Pluma 1 , Laia Codó 19 , Andrés García-Montero 20 , Josep Manyé 3 , Javier P Gisbert 4, 16 , Sara Marsal 1 , Antonio Julià 1
The Pharmacogenomics Journal ( IF 2.9 ) Pub Date : 2019-05-02 , DOI: 10.1038/s41397-019-0090-4 Adrià Aterido 1, 2 , Núria Palau 1 , Eugeni Domènech 3, 4 , Pilar Nos Mateu 4, 5 , Ana Gutiérrez 4, 6 , Fernando Gomollón 4, 7 , Juan L Mendoza 8 , Esther Garcia-Planella 9 , Manuel Barreiro-de Acosta 10 , Fernando Muñoz 11 , Maribel Vera 12 , Cristina Saro 13 , Maria Esteve 4, 14 , Montserrat Andreu 15 , María Chaparro 4, 16 , Julián Panés 4, 17 , Valle García-Sánchez 18 , María López-Lasanta 1 , Andrea Pluma 1 , Laia Codó 19 , Andrés García-Montero 20 , Josep Manyé 3 , Javier P Gisbert 4, 16 , Sara Marsal 1 , Antonio Julià 1
Affiliation
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The production of antibodies to anti-tumor necrosis factor alpha (TNF) agents is one of the main causes of treatment failure in Crohn's disease (CD). To date, however, the contribution of genetics to anti-TNF immunogenicity in CD is still unknown. The objective of the present study was to identify genetic variation associated with anti-TNF immunogenicity in CD. We performed a two-stage genome-wide association study in a cohort of 96 and 123 adalimumab-treated patients, respectively. In the discovery stage, we identified a genome-wide significant association between the CD96 locus and the production of antibodies to anti-TNF treatment (P = 1.88e-09). This association was validated in the replication stage (P < 0.05). The risk allele for anti-TNF immunogenicity was found to be also associated with a lack of response to anti-TNF therapy (P = 0.019). These findings represent an important step toward the understanding of the immunogenicity-based mechanisms that underlie anti-TNF response in CD.
中文翻译：
CD96 基因座与克罗恩病抗 TNF 治疗的免疫原性之间的遗传关联。
产生抗肿瘤坏死因子α (TNF) 药物的抗体是克罗恩病 (CD) 治疗失败的主要原因之一。然而，迄今为止，遗传学对 CD 中抗 TNF 免疫原性的贡献仍然未知。本研究的目的是确定与 CD 中抗 TNF 免疫原性相关的遗传变异。我们分别对 96 名和 123 名接受阿达木单抗治疗的患者进行了两阶段的全基因组关联研究。在发现阶段，我们确定了 CD96 基因座与抗 TNF 治疗抗体产生之间的全基因组显着关联 (P = 1.88e-09)。这种关联在复制阶段得到了验证（P < 0.05）。发现抗 TNF 免疫原性的风险等位基因也与抗 TNF 治疗缺乏反应有关（P = 0. 019)。这些发现代表了朝着理解作为 CD 中抗 TNF 反应基础的基于免疫原性的机制迈出的重要一步。
更新日期：2019-11-18
中文翻译：
CD96 基因座与克罗恩病抗 TNF 治疗的免疫原性之间的遗传关联。
产生抗肿瘤坏死因子α (TNF) 药物的抗体是克罗恩病 (CD) 治疗失败的主要原因之一。然而，迄今为止，遗传学对 CD 中抗 TNF 免疫原性的贡献仍然未知。本研究的目的是确定与 CD 中抗 TNF 免疫原性相关的遗传变异。我们分别对 96 名和 123 名接受阿达木单抗治疗的患者进行了两阶段的全基因组关联研究。在发现阶段，我们确定了 CD96 基因座与抗 TNF 治疗抗体产生之间的全基因组显着关联 (P = 1.88e-09)。这种关联在复制阶段得到了验证（P < 0.05）。发现抗 TNF 免疫原性的风险等位基因也与抗 TNF 治疗缺乏反应有关（P = 0. 019)。这些发现代表了朝着理解作为 CD 中抗 TNF 反应基础的基于免疫原性的机制迈出的重要一步。
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