Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Uppsala University Hospital, Uppsala, Sweden.
Front Immunol. 2021 May 14;12:685312. doi: 10.3389/fimmu.2021.685312. eCollection 2021.
Measurement of two groups of autoantibodies, rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) have gained increasing significance in the diagnosis and classification of rheumatoid arthritis (RA) over the last 65 years. Despite this rising importance of autoimmune serology in RA, there is a palpable lack of harmonization between different commercial RF and ACPA tests. While a minimal diagnostic specificity has been defined for RF tests, which almost always are related to an international reference preparation, neither of this applies to ACPA. Especially assays with low diagnostic specificity are associated with very low positive predictive values or post-test probabilities in real world settings. In this review we focus on issues of practical bearing for the clinical physician diagnosing patients who potentially have RA, or treating patients diagnosed with RA. We advocate that all clinically used assays for RF and ACPA should be aligned to a common diagnostic specificity of 98-99% compared to healthy controls. This high and rather narrow interval corresponds to the diagnostic specificity seen for many commercial ACPA tests, and represents a specificity that is higher than what is customary for most RF assays. Data on antibody occurrence harmonized in this way should be accompanied by test result-specific likelihood ratios for the target diagnosis RA on an ordinal or interval scale, which will provide the clinical physician with more granular and richer information than merely relating numerical values to a single cut-off point. As many physicians today are used to evaluate autoantibodies as positive or negative on a nominal scale, the introduction of test result-specific likelihood ratios will require a change in clinical mindset. We also discuss the use of autoantibodies to prognosticate future arthritis development in at-risk patients as well as predict severe disease course and outcome of pharmacological treatment.
在过去的 65 年中，测量两组自身抗体，类风湿因子 (RF) 和抗瓜氨酸化蛋白/肽抗体 (ACPA)，在类风湿关节炎 (RA) 的诊断和分类中变得越来越重要。尽管自身免疫血清学在 RA 中的重要性不断提高，但不同商业 RF 和 ACPA 检测之间明显缺乏协调。虽然已经为 RF 检测定义了最小的诊断特异性，这些检测几乎总是与国际参考制剂相关，但 ACPA 则不然。特别是诊断特异性低的检测在真实环境中与非常低的阳性预测值或后验概率相关。在这篇综述中，我们重点关注对诊断潜在 RA 患者或治疗已确诊 RA 患者的临床医生具有实际意义的问题。我们主张，所有用于 RF 和 ACPA 的临床检测都应与健康对照相比，达到 98-99%的共同诊断特异性。这个高而相当窄的区间与许多商业 ACPA 检测的诊断特异性相对应，并且代表了比大多数 RF 检测通常更高的特异性。以这种方式协调的抗体发生数据应附有针对目标诊断 RA 的检测结果特异性似然比，该比然比将为临床医生提供比仅仅将数值与单个截止值相关联更具粒度和更丰富的信息。由于当今许多医生习惯于在名义尺度上评估自身抗体是阳性还是阴性，因此引入检测结果特异性似然比将需要改变临床思维。我们还讨论了使用自身抗体来预测高危患者未来关节炎的发展，以及预测严重疾病过程和药物治疗结果。
