风湿性疾病患者队列中HLA单倍型与抗药抗体产生之间的相关性。
Correlation between HLA haplotypes and the development of antidrug antibodies in a cohort of patients with rheumatic diseases.
作者信息
Benucci Maurizio, Damiani Arianna, Li Gobbi Francesca, Bandinelli Francesca, Infantino Maria, Grossi Valentina, Manfredi Mariangela, Noguier Guillaume, Meacci Francesca
机构信息
Rheumatology Unit.
Immunology and Allergology Laboratory Unit, USL-Toscana Centro, Hospital S. Giovanni di Dio, Florence, Italy.
出版信息
Biologics. 2018 Jan 31;12:37-41. doi: 10.2147/BTT.S145941. eCollection 2018.
INTRODUCTION
The aim of this study was to investigate the correlation between human leukocyte antigen (HLA) haplotypes and the development of antidrug antibodies (ADAs) in a cohort of patients with rheumatic diseases.
PATIENTS AND METHODS
We evaluated the presence of ADAs in 248 patients with inflammatory rheumatic diseases after 6 months of treatment with anti-TNF drugs: 26 patients were treated with infliximab (IFX; three with rheumatoid arthritis [RA], 13 with ankylosing spondylitis [AS], 10 with psoriatic arthritis [PsA]); 83 treated with adalimumab (ADA; 24 with RA, 36 with AS, 23 with PsA); 88 treated with etanercept (ETA; 35 with RA, 27 with AS, 26 with PsA); 32 treated with certolizumab (CERT; 25 with RA, two with AS, five with PsA); and 19 treated with golimumab (GOL; three with RA, seven with AS, nine with PsA). Serum drug and ADA levels were determined using Lisa-Tracker Duo, the ADA-positive samples underwent an inhibition test, and the true-positive samples underwent genetic HLA typing. To have a homogeneous control population, we also performed genetic HLA typing of 11 ADA-negative patients.
RESULTS
After inhibition test, the frequency of ADAs was 2/26 patients treated with IFX (7.69%), 4/83 treated with ADA (4.81%), 0/88 treated with ETA (0%), 4/32 treated with CERT (12.5%), and 1/19 treated with GOL (5.26%). The frequency of HLA alleles in the examined patients was HLA-DRβ-11 0.636, HLA-DQ-03 0.636, and HLA-DQ-05 0.727. The estimated relative risks between the ADA-positive patients and the ADA-negative patients were HLA-DRβ-11 2.528 (95% CI 0.336-19.036), HLA-DQ-03 1.750 (95% CI 0.289-10.581), and HLA-DQ-05 2.424 (95% CI 0.308-15.449).
CONCLUSION
This is the first study that shows an association between HLA and genetic factors associated with the occurrence of ADAs in patients with rheumatic diseases, but the number of samples is too small to draw any definite conclusion.
引言
本研究旨在调查一组风湿性疾病患者中人类白细胞抗原（HLA）单倍型与抗药抗体（ADA）产生之间的相关性。
患者与方法
我们评估了248例炎性风湿性疾病患者在接受抗TNF药物治疗6个月后ADA的存在情况：26例患者接受英夫利昔单抗（IFX）治疗（3例类风湿关节炎[RA]、13例强直性脊柱炎[AS]、10例银屑病关节炎[PsA]）；83例接受阿达木单抗（ADA）治疗（24例RA、36例AS、23例PsA）；88例接受依那西普（ETA）治疗（35例RA、27例AS、26例PsA）；32例接受赛妥珠单抗（CERT）治疗（25例RA、2例AS、5例PsA）；19例接受戈利木单抗（GOL）治疗（3例RA、7例AS、9例PsA）。使用Lisa-Tracker Duo测定血清药物和ADA水平，对ADA阳性样本进行抑制试验，对真阳性样本进行HLA基因分型。为了获得同质对照人群，我们还对11例ADA阴性患者进行了HLA基因分型。
结果
抑制试验后，接受IFX治疗的26例患者中有2例（7.69%）出现ADA，接受ADA治疗的83例中有4例（4.81%），接受ETA治疗的88例中为0例（0%），接受CERT治疗的32例中有4例（12.5%），接受GOL治疗的19例中有1例（5.26%）。所检查患者中HLA等位基因的频率为HLA-DRβ-11 0.636、HLA-DQ-03 0.636和HLA-DQ-05 0.727。ADA阳性患者与ADA阴性患者之间的估计相对风险为HLA-DRβ-11 2.528（95%CI 0.336 - 19.036）、HLA-DQ-03 1.750（95%CI 0.289 - 10.581）和HLA-DQ-05 2.424（95%CI 0.308 - 15.449）。
结论
这是第一项表明HLA与风湿性疾病患者中ADA发生相关的遗传因素之间存在关联的研究，但样本数量太少，无法得出任何明确结论。
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