Association of valine and leucine at HLA-DRB1 position 11 with radiographic progression in rheumatoid arthritis, independent of the shared epitope alleles but not independent of anti-citrullinated protein antibodies.
Association of valine and leucine at HLA-DRB1 position 11 with radiographic progression in rheumatoid arthritis, independent of the shared epitope alleles but not independent of anti-citrullinated protein antibodies.
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HLA-DRB1 位点 11 的缬氨酸和亮氨酸与类风湿性关节炎的放射学进展相关，独立于共享表位等位基因，但不独立于抗瓜氨酸蛋白抗体。
DOI：
10.1002/art.39018
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
vanderHelm-vanMil,AHM
中科院分区：
文献类型：
--
作者：
vanSteenbergen,HW;Raychaudhuri,S;Rodríguez-Rodríguez,L;Rantapää-Dahlqvist,S;Berglin,E;Toes,REM;Huizinga,TWJ;Fernández-Gutiérrez,B;Gregersen,PK;vanderHelm-vanMil,AHM
目的HLA-DRB 1共享表位（SE）等位基因与类风湿关节炎（RA）发生、发展的危险性增加有关。最近，获得了对易于RA发展的HLA分子的肽结合沟的变化的新见解：HLA-DRβ1中的11位（缬氨酸和亮氨酸），HLA-B中的9位（天冬氨酸）和HLA-DPβ1中的9位（苯丙氨酸）。本研究调查了这些变异是否也与RA的放射学进展相关，与SE状态和ACPA无关。方法对1,878例RA患者的4,911个X线片集进行了研究，这些患者包括Leiden-EAC（荷兰）、Umeillance（瑞典）、HCSC-RAC（西班牙）和NDB（美国）队列。使用免疫芯片的SNP数据插补HLA，并使用加性模型测试每个队列与放射学进展相关的所提及的氨基酸。使用固定效应模型，将四个队列的结果合并到逆方差加权荟萃分析中。分析以SE状态和抗瓜氨酸肽抗体（ACPA）为条件。结果HLA-DRβ1 11位的缬氨酸和亮氨酸与更多的放射学进展相关（荟萃分析p= 5.11 x10（-7））;该效应与SE状态无关（荟萃分析p= 0.022），但与ACPA无关。HLA-DPβ1第9位的天冬氨酸与更严重的放射学进展相关（荟萃分析p= 0.024），但并非独立于SE状态。HLA-B第9位的苯丙氨酸与放射学进展无关。结论HLA-DRβ1位点11位的缬氨酸和亮氨酸具有较高的放射学进展风险，与SE状态无关，但与ACPA无关。这支持了位置11处的这些氨基酸的相关性。本文受版权保护。All rights reserved.
Objective For decades it has been known that the HLA-DRB1 Shared Epitope (SE) alleles are associated with an increased risk on development and progression of rheumatoid arthritis (RA). Recently, new insights into variations in the peptide-binding grooves of HLA-molecules that predispose to RA-development are obtained: position 11 in HLA-DRβ1 (Valine and Leucine), position 9 in HLA-B (Aspartic acid) and position 9 in HLA-DPβ1 (Phenylalanine). This study investigated whether these variants also associate with radiographic progression within RA, independent of SE-status and ACPA. Methods In total 4,911 radiograph-sets of 1,878 RA-patients, included in the Leiden-EAC (Netherlands), Umeå (Sweden), HCSC-RAC (Spain) and NDB (USA) cohorts, were studied. HLA was imputed using SNP-data of the Immunochip and the mentioned amino acids were tested in relation to radiographic progression per cohort using an additive model. Results of the four cohorts were combined in inverse-variance weighted meta-analyses using a fixed effects model. Analyses were conditioned on SE-status and anti-citrullinated-peptide antibodies (ACPA). Results Valine and Leucine at HLA-DRβ1 position 11 associated with more radiographic progression (meta-analysis p= 5.11 x10 (-7)); this effect was independent of SE-status (meta-analysis p= 0.022) but not independent of ACPA. Aspartic acid at HLA-DPβ1 position 9 associated with more severe radiographic progression (meta-analysis p= 0.024), though not independent of SE-status. Phenylalanine at HLA-B position 9 was not associated with radiographic progression. Conclusion Valine and Leucine at HLA-DRβ1 position 11 conferred risk to a higher rate of radiographic progression independent of SE-status but not independent of ACPA. This supports the relevance of these amino acids at position 11. This article is protected by copyright. All rights reserved.
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作者：
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