在德国一个多中心的早期关节炎全国队列中，对未修饰和相应瓜氨酸化自身抗原的 IgG 抗体进行分析。
Profiling of IgG antibodies targeting unmodified and corresponding citrullinated autoantigens in a multicenter national cohort of early arthritis in Germany.
机构信息
Department Rheumatology & Hiller Research Unit, UKD, Heinrich-Heine-University Düsseldorf, Merowingerplatz 1a, 40225, Düsseldorf, Germany.
Protagen AG (now Oncimmune Germany GmbH), Otto-Hahn-Str. 15, 44227, Dortmund, Germany.
出版信息
Arthritis Res Ther. 2020 Jul 6;22(1):167. doi: 10.1186/s13075-020-02252-6.
OBJECTIVE
To assess the diagnostic potential of IgG antibodies to citrullinated and corresponding native autoantigens in early arthritis.
METHODS
IgG autoantibodies to 390 distinct unmodified and corresponding in vitro citrullinated recombinant proteins were measured by a multiplex assay in baseline blood samples from a German multicenter national cohort of 411 early arthritis patients (56.5 ± 14.6 years, 62.8% female). The cohort was randomly split into a training cohort (n = 329, 28.6% ACPA positive) and a validation cohort (n = 82, 32.9% ACPA pos.). The diagnostic properties of candidate antibodies to predict a subsequent diagnosis of rheumatoid arthritis (RA) as opposed to a non-RA diagnosis were assessed by receiver operating characteristics analysis and generalized linear modeling (GLM) with Bonferroni correction in comparison to clinically determined IgM rheumatoid factor (RF) and citrullinated peptide antibody (ACPA) status.
RESULTS
Of 411 patients, 309 (75.2%) were classified as RA. Detection rates of antibody responses to citrullinated and uncitrullinated forms of the proteins were weakly correlated (Spearman's r = 0.13 (95% CI 0.029-0.22), p = 0.01). The concentration of 34 autoantibodies (32 to citrullinated and 2 to uncitrullinated antigens) was increased at least 2-fold in RA patients and further assessed. In the training cohort, a significant association of citrullinated "transformer 2 beta homolog" (cTRA2B)-IgG with RA was observed (OR 5.3 × 10, 95% CI 0.8 × 10-3.0 × 10, p = 0.047). Sensitivity and specificity of cTRA2B-IgG (51.0%/82.9%) were comparable to RF (30.8%/91.6%) or ACPA (32.1%/94.7%). Similar results were obtained in the validation cohort. The addition of cTRA2B-IgG to ACPA improved the diagnostic performance over ACPA alone (p = 0.026 by likelihood ratio test).
CONCLUSIONS
cTRA2B-IgG has the potential to improve RA diagnosis in conjunction with RF and ACPA in early arthritis.
目的
评估 IgG 抗体对瓜氨酸化和相应天然自身抗原在早期关节炎中的诊断潜力。
方法
采用多指标分析方法，检测来自德国多中心全国 411 例早期关节炎患者（56.5±14.6 岁，62.8%为女性）基线血液样本中针对 390 种不同未修饰和相应体外瓜氨酸化重组蛋白的 IgG 自身抗体。该队列被随机分为训练队列（n=329，28.6% ACPA 阳性）和验证队列（n=82，32.9% ACPA 阳性）。通过接收者工作特征分析和广义线性建模（GLM），并与临床确定的 IgM 类风湿因子（RF）和瓜氨酸肽抗体（ACPA）状态进行比较，评估候选抗体预测随后类风湿关节炎（RA）诊断而非非 RA 诊断的诊断特性。
结果
在 411 例患者中，309 例（75.2%）被归类为 RA。瓜氨酸化和非瓜氨酸化形式的蛋白抗体反应的检出率呈弱相关（Spearman r=0.13（95%CI 0.029-0.22），p=0.01）。在 RA 患者中，34 种自身抗体（32 种针对瓜氨酸化抗原，2 种针对非瓜氨酸化抗原）的浓度增加了至少 2 倍，并进一步进行了评估。在训练队列中，观察到瓜氨酸化“转录因子 2β 同源物”（cTRA2B）-IgG 与 RA 显著相关（OR 5.3×10，95%CI 0.8×10-3.0×10，p=0.047）。cTRA2B-IgG 的敏感性和特异性（51.0%/82.9%）与 RF（30.8%/91.6%）或 ACPA（32.1%/94.7%）相当。在验证队列中也得到了类似的结果。与 ACPA 相比，cTRA2B-IgG 的添加可提高诊断性能（似然比检验 p=0.026）。
结论
cTRA2B-IgG 具有与 RF 和 ACPA 联合用于早期关节炎 RA 诊断的潜力。
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