南非类风湿性关节炎患者中免疫球蛋白A、类风湿因子及抗瓜氨酸化肽自身抗体的诊断效用,以及烟草使用和遗传易感性对它们的影响
Diagnostic utility of, and influence of tobacco usage and genetic predisposition on, immunoglobulin A, rheumatoid factor and anti-citrullinated peptide auto-antibodies in South African rheumatoid arthritis patients.
作者信息
Meyer Pieter, Ally Mahmood, Hodkinson Bridget, Anderson Ronald, Tikly Mohammed
机构信息
University of Pretoria, Immunology; NHLS, Immunology.
University of Pretoria, Internal Medicine.
出版信息
Afr Health Sci. 2018 Jun;18(2):295-303. doi: 10.4314/ahs.v18i2.14.
BACKGROUND
The immunoglobulin A isotypes of anti-cyclic citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) are associated with disease severity and progression in Caucasian rheumatoid arthritis (RA) patients, as well as with genetic predisposition and tobacco use.
OBJECTIVES
To compare levels of ACPA-IgA and RF-IgA with those of ACPA-IgG and cRF in a cohort of black South African RA patients and healthy controls.To investigate the relationship between IGA autoantibodies and disease severity, genetic predisposition and tobacco use.
METHODS
RF-IgA and ACPA-IgA were determined in a cohort of predominantly black South African RA patients (n=75) in relation to serodiagnostic and prognostic potential, as well as tobacco use and genetic predisposition. Healthy control subjects were included to determine sensitivity, specificity and predictive values.ACPA-IgG/IgA and RF-IgA were determined by enzyme immunoassay and hs-CRP and cRF by nephelometry. Cotinine levels were determined by ELISA.
RESULTS
The frequencies of ACPA-IgA and RF-IgA were 31% and 88% respectively compared to 88% for both types of traditional autoantibody procedures. ACPA-IgA was significantly higher (p=0.007) in patients with short disease duration, while linear regression analysis revealed a positive relationship with baseline disease activity scores. Levels of ACPA-IgG and ACPA-IgA were significantly higher in tobacco users who carried the HLA shared epitope.
CONCLUSION
Although lacking in serodiagnostic superiority over cRF and ACPA-IgG, inclusion of RF-IgA and ACPA-IgA in autoantibody panels may provide insights into disease pathogenesis, interactions between tobacco usage and HLA genotype in the production of potentially disease-triggering ACPA-IgA antibodies.
背景
抗环瓜氨酸肽抗体(ACPA)和类风湿因子(RF)的免疫球蛋白A亚型与白种人类风湿关节炎(RA)患者的疾病严重程度和进展相关,也与遗传易感性和吸烟有关。
目的
比较南非黑人RA患者队列和健康对照中ACPA-IgA和RF-IgA与ACPA-IgG和cRF的水平。研究IgA自身抗体与疾病严重程度、遗传易感性和吸烟之间的关系。
方法
在以南非黑人为主的RA患者队列(n = 75)中测定RF-IgA和ACPA-IgA,评估其血清学诊断和预后潜力,以及与吸烟和遗传易感性的关系。纳入健康对照以确定敏感性、特异性和预测值。通过酶免疫测定法测定ACPA-IgG/IgA和RF-IgA,通过散射比浊法测定hs-CRP和cRF。通过ELISA测定可替宁水平。
结果
ACPA-IgA和RF-IgA的频率分别为31%和88%,而两种传统自身抗体检测方法的频率均为88%。疾病病程短的患者中ACPA-IgA显著更高(p = 0.007),线性回归分析显示其与基线疾病活动评分呈正相关。携带HLA共享表位的吸烟者中ACPA-IgG和ACPA-IgA水平显著更高。
结论
尽管RF-IgA和ACPA-IgA在血清学诊断上并不优于cRF和ACPA-IgG,但将它们纳入自身抗体检测组合可能有助于深入了解疾病发病机制,以及吸烟与HLA基因型在产生潜在疾病触发ACPA-IgA抗体过程中的相互作用。