Zanussi Jacy T, Zhao Juan, Wei Wei-Qi, Karakoc Gul, Chung Cecilia P, Feng QiPing, Olsen Nancy J, Stein C Michael, Kawai Vivian K
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA.
BMC Rheumatol. 2023 Aug 7;7(1):24. doi: 10.1186/s41927-023-00349-4.
Antinuclear antibodies (ANA) are antibodies present in several autoimmune disorders. However, a large proportion of the general population (20%) also have a positive test; very few of these individuals will develop an autoimmune disease, and the clinical impact of a positive ANA in them is not known. Thus, we test the hypothesis that ANA + test reflects a state of immune dysregulation that alters risk for some clinical disorders in individuals without an autoimmune disease.
We performed high throughput association analyses in a case-control study using real world data from the de-identified electronic health record (EHR) system from Vanderbilt University Medical Center. The study population included individuals with an ANA titer ≥ 1:80 at any time (ANA +) and those with negative results (ANA-). The cohort was stratified into sub-cohorts of individuals with and without an autoimmune disease. A phenome-wide association study (PheWAS) adjusted by sex, year of birth, race, and length of follow-up was performed in the study cohort and in the sub-cohorts. As secondary analyses, only clinical diagnoses after ANA testing were included in the analyses.
The cohort included 70,043 individuals: 49,546 without and 20,497 with an autoimmune disease, 26,579 were ANA + and 43,464 ANA-. In the study cohort and the sub-cohort with autoimmune disease, ANA + was associated (P ≤ 5 × 10) with 88 and 136 clinical diagnoses respectively, including lupus (OR ≥ 5.4, P ≤ 7.8 × 10) and other autoimmune diseases and complications. In the sub-cohort without autoimmune diseases, ANA + was associated with increased risk of Raynaud's syndrome (OR ≥ 2.1) and alveolar/perialveolar-related pneumopathies (OR ≥ 1.4) and decreased risk of hepatitis C, tobacco use disorders, mood disorders, convulsions, fever of unknown origin, and substance abuse disorders (OR ≤ 0.8). Analyses including only diagnoses after ANA testing yielded similar results.
A positive ANA test, in addition to known associations with autoimmune diseases, Raynaud's phenomenon, and idiopathic fibrosing alveolitis related disorders, is associated with decreased prevalence of several non-autoimmune diseases.
抗核抗体（ANA）存在于多种自身免疫性疾病中。然而，很大一部分普通人群（20%）的检测结果也呈阳性；这些个体中很少有人会发展为自身免疫性疾病，而且其ANA检测呈阳性的临床影响尚不清楚。因此，我们检验了这样一个假设，即ANA检测阳性反映了一种免疫失调状态，这种状态会改变无自身免疫性疾病个体患某些临床疾病的风险。
我们在一项病例对照研究中使用范德堡大学医学中心去识别化电子健康记录（EHR）系统的真实世界数据进行了高通量关联分析。研究人群包括任何时候ANA滴度≥1:80的个体（ANA阳性）和检测结果为阴性的个体（ANA阴性）。该队列被分层为有和无自身免疫性疾病的亚队列。在研究队列和亚队列中进行了一项按性别、出生年份、种族和随访时间调整的全表型关联研究（PheWAS）。作为次要分析，分析中仅纳入ANA检测后的临床诊断。
该队列包括70,043名个体：49,546名无自身免疫性疾病个体和20,497名有自身免疫性疾病个体，26,579名ANA阳性和43,464名ANA阴性。在研究队列和有自身免疫性疾病的亚队列中，ANA阳性分别与88种和136种临床诊断相关（P≤5×10），包括狼疮（OR≥5.4，P≤7.8×10）以及其他自身免疫性疾病和并发症。在无自身免疫性疾病的亚队列中，ANA阳性与雷诺综合征风险增加（OR≥2.1）和肺泡/肺泡周围相关肺病风险增加（OR≥1.4）相关，而丙型肝炎、烟草使用障碍、情绪障碍、惊厥、不明原因发热和物质滥用障碍风险降低（OR≤0.8）。仅纳入ANA检测后诊断的分析得出了类似结果。
ANA检测阳性，除了与已知的自身免疫性疾病、雷诺现象和特发性纤维化肺泡炎相关疾病有关外，还与几种非自身免疫性疾病的患病率降低有关。
