Nogueira Leonor, Parra Emilie, Larrieu Margaux, Verrouil Evelyne, Cornillet Martin
Laboratory of Cell Biology and Cytology University Hospital of Toulouse Toulouse France.
Clin Transl Immunology. 2021 Jul 5;10(7):e1288. doi: 10.1002/cti2.1288. eCollection 2021.
In rheumatoid arthritis (RA), antibodies to citrullinated protein (ACPA) are believed to be heterogeneous and patient stratification by antibody profiling raised clinical interest for patient management. However, heterogeneity might be partially artificial because of the use of heterogeneous methods for ACPA detection. In recent work instead, we found that ACPA were mainly directed towards a single fibrin-derived peptide, β60-74BiotNt, but a comparative analysis with the presence of other ACPA specificities is still lacking.
To present an overview of RA patients' stratification based on the detection of the main ACPA fine specificities with the same method as compared to that of anti-β60-74BiotNt antibodies.
Over 4500 measurements were performed with more than 22 standardised ELISAs, sera from 180 RA patients and 200 to 436 non-RA rheumatic disease controls.
Four to 81% of RA patients had ACPA towards various targets, confirming the heterogeneity of ACPA specificities. However, the subgroups of patients overlapped up to 97% with ACPA levels of correlation coefficients up to 0.8, showing redundancy of some targets. Multiplexing decreased diagnostic specificity from 95% to 64%. Instead, anti-β60-74BiotNt detection identified almost all ACPA-positive patients.
Antibodies to citrullinated protein multiplexing shows some degree of redundancy and is not suitable for diagnostic purposes. ACPA fine specificities might be less heterogeneous than perceived by sera testing on multiple peptides. Patient stratification largely depends on detection methods and requires standardisation.
在类风湿关节炎（RA）中，瓜氨酸化蛋白抗体（ACPA）被认为具有异质性，通过抗体谱对患者进行分层引起了临床对患者管理的关注。然而，由于使用了异质性的ACPA检测方法，这种异质性可能部分是人为造成的。相反，在最近的研究中，我们发现ACPA主要针对一种单一的纤维蛋白衍生肽β60 - 74BiotNt，但仍缺乏与其他ACPA特异性存在情况的比较分析。
与抗β60 - 74BiotNt抗体相比，基于用相同方法检测主要ACPA精细特异性，对RA患者分层进行概述。
使用22种以上标准化酶联免疫吸附测定（ELISA）对180例RA患者和200至436例非RA风湿性疾病对照的血清进行了超过4500次检测。
4%至81%的RA患者具有针对各种靶标的ACPA，证实了ACPA特异性的异质性。然而，患者亚组之间的重叠率高达97%，ACPA水平的相关系数高达0.8，表明一些靶标存在冗余。多重检测使诊断特异性从95%降至64%。相反，抗β60 - 74BiotNt检测几乎识别出所有ACPA阳性患者。
瓜氨酸化蛋白多重抗体检测显示出一定程度的冗余，不适用于诊断目的。ACPA精细特异性可能不如对多种肽进行血清检测所认为的那样具有异质性。患者分层在很大程度上取决于检测方法，需要标准化。
