HLA-DRB1 共享表位等位基因与免疫检查点抑制剂诱导的炎症性关节炎的关联。
Association of HLA-DRB1 shared epitope alleles and immune checkpoint inhibitor-induced inflammatory arthritis.
机构信息
Division of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
School of Life Sciences, Pharmacy & Chemistry, Kingston University London, London, UK.
出版信息
Rheumatology (Oxford). 2019 Mar 1;58(3):476-480. doi: 10.1093/rheumatology/key358.
OBJECTIVE
To evaluate the frequency of HLA class I and II alleles associated with traditional forms of inflammatory arthritis in patients with immune checkpoint inhibitor (ICI)-induced inflammatory arthritis as compared with population controls.
METHODS
High-resolution HLA typing was performed on 27 patients with ICI-induced inflammatory arthritis and 726 healthy controls. Genotyping at the shared epitope (SE) locus (HLA DRB1) was performed on 220 RA cases. Allele-positivity rates and frequency of having at least one SE allele were compared using Fisher's exact test between ICI-induced inflammatory arthritis and healthy controls. Frequency of having at least one SE allele was also compared between ICI-induced inflammatory arthritis and RA cases.
RESULTS
Twenty-six patients with ICI-induced inflammatory arthritis were of European descent, and one was African American. In those 26 patients, 16 (61.5%) had at least one SE allele, significantly different from healthy controls of European descent, in whom 299 (41.2%) had at least one SE allele (odds ratio 2.3, P = 0.04). The allele-positivity rate of DRB1*04: 05 was also higher in the ICI-induced inflammatory arthritis group. The ICI-induced inflammatory arthritis population and RA patients of European descent did not differ in frequency of having at least one SE allele, but ICI-induced inflammatory arthritis patients were more likely to be autoantibody-negative for RF and anti-CCP antibodies.
CONCLUSION
Patients with ICI-induced inflammatory arthritis of European descent were more likely to have at least one SE allele than healthy controls. Further studies are needed to validate these findings and investigate whether a unique immunogenetic framework increases risk for different immune-related adverse events.
目的
评估与人群对照相比，免疫检查点抑制剂（ICI）诱导的炎症性关节炎患者中与传统炎症性关节炎形式相关的 HLA Ⅰ类和Ⅱ类等位基因的频率。
方法
对 27 例 ICI 诱导的炎症性关节炎患者和 726 名健康对照者进行高分辨率 HLA 分型。对 220 例 RA 患者进行共享表位（SE）位点（HLA-DRB1）基因分型。采用 Fisher 确切检验比较 ICI 诱导的炎症性关节炎与健康对照组之间的等位基因阳性率和至少有一个 SE 等位基因的频率。还比较了 ICI 诱导的炎症性关节炎与 RA 患者之间至少有一个 SE 等位基因的频率。
结果
26 例 ICI 诱导的炎症性关节炎患者为欧洲血统，1 例为非裔美国人。在这 26 例患者中，有 16 例（61.5%）至少有一个 SE 等位基因，与具有至少一个 SE 等位基因的欧洲血统健康对照组（299 例[41.2%]）明显不同（比值比 2.3，P = 0.04）。DRB1*04:05 等位基因的阳性率在 ICI 诱导的炎症性关节炎组也较高。ICI 诱导的炎症性关节炎人群和欧洲血统的 RA 患者在至少有一个 SE 等位基因的频率上没有差异，但 ICI 诱导的炎症性关节炎患者更可能对 RF 和抗 CCP 抗体呈自身抗体阴性。
结论
欧洲血统的 ICI 诱导的炎症性关节炎患者比健康对照者更有可能至少有一个 SE 等位基因。需要进一步的研究来验证这些发现，并研究是否独特的免疫遗传框架增加了发生不同免疫相关不良事件的风险。
Zotero 插件