类风湿关节炎病例和非类风湿关节炎对照中电子病历里自身抗体、自身免疫风险等位基因与临床诊断之间的关联。
Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and non-rheumatoid arthritis controls.
作者信息
Liao Katherine P, Kurreeman Fina, Li Gang, Duclos Grant, Murphy Shawn, Guzman Raul, Cai Tianxi, Gupta Namrata, Gainer Vivian, Schur Peter, Cui Jing, Denny Joshua C, Szolovits Peter, Churchill Susanne, Kohane Isaac, Karlson Elizabeth W, Plenge Robert M
机构信息
Brigham and Women's Hospital, 75 Francis Street, PBB-B3, Boston, MA 02115, USA.
出版信息
Arthritis Rheum. 2013 Mar;65(3):571-81. doi: 10.1002/art.37801.
OBJECTIVE
The significance of non-rheumatoid arthritis (RA) autoantibodies in patients with RA is unclear. The aim of this study was to assess associations of autoantibodies with autoimmune risk alleles and with clinical diagnoses from the electronic medical records (EMRs) among RA cases and non-RA controls.
METHODS
Data on 1,290 RA cases and 1,236 non-RA controls of European genetic ancestry were obtained from the EMRs of 2 large academic centers. The levels of anti-citrullinated protein antibodies (ACPAs), antinuclear antibodies (ANAs), anti-tissue transglutaminase antibodies (AGTAs), and anti-thyroid peroxidase (anti-TPO) antibodies were measured. All subjects were genotyped for autoimmune risk alleles, and the association between number of autoimmune risk alleles present and number of types of autoantibodies present was studied. A phenome-wide association study (PheWAS) was conducted to study potential associations between autoantibodies and clinical diagnoses among RA cases and non-RA controls.
RESULTS
The mean ages were 60.7 years in RA cases and 64.6 years in non-RA controls. The proportion of female subjects was 79% in each group. The prevalence of ACPAs and ANAs was higher in RA cases compared to controls (each P < 0.0001); there were no differences in the prevalence of anti-TPO antibodies and AGTAs. Carriage of higher numbers of autoimmune risk alleles was associated with increasing numbers of autoantibody types in RA cases (P = 2.1 × 10(-5)) and non-RA controls (P = 5.0 × 10(-3)). From the PheWAS, the presence of ANAs was significantly associated with a diagnosis of Sjögren's/sicca syndrome in RA cases.
CONCLUSION
The increased frequency of autoantibodies in RA cases and non-RA controls was associated with the number of autoimmune risk alleles carried by an individual. PheWAS of EMR data, with linkage to laboratory data obtained from blood samples, provide a novel method to test for the clinical significance of biomarkers in disease.
目的
类风湿关节炎（RA）患者中非类风湿关节炎自身抗体的意义尚不清楚。本研究旨在评估RA病例和非RA对照中自身抗体与自身免疫风险等位基因以及电子病历（EMR）临床诊断之间的关联。
方法
从2个大型学术中心的EMR中获取1290例欧洲遗传血统的RA病例和1236例非RA对照的数据。检测抗瓜氨酸化蛋白抗体（ACPA）、抗核抗体（ANA）、抗组织转谷氨酰胺酶抗体（AGTA）和抗甲状腺过氧化物酶（抗TPO）抗体的水平。对所有受试者进行自身免疫风险等位基因基因分型，研究存在的自身免疫风险等位基因数量与存在的自身抗体类型数量之间的关联。进行全表型关联研究（PheWAS）以研究RA病例和非RA对照中自身抗体与临床诊断之间的潜在关联。
结果
RA病例的平均年龄为60.7岁，非RA对照为64.6岁。每组女性受试者比例均为79%。与对照组相比，RA病例中ACPA和ANA的患病率更高（均P<0.0001）；抗TPO抗体和AGTA的患病率无差异。在RA病例（P=2.1×10⁻⁵）和非RA对照（P=5.0×10⁻³）中，携带更多自身免疫风险等位基因与自身抗体类型数量增加相关。从PheWAS结果来看，ANA的存在与RA病例中的干燥综合征/口干症诊断显著相关。
结论
RA病例和非RA对照中自身抗体频率增加与个体携带的自身免疫风险等位基因数量相关。将EMR数据与从血样获得的实验室数据相联系的PheWAS，提供了一种检测生物标志物在疾病中临床意义的新方法。
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