Anti-Carbamylated Protein Antibodies in ACPA-Negative and ACPA-Positive Patients with Rheumatoid Arthritis

IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Doklady Biochemistry and Biophysics Pub Date : 2024-07-13 DOI:10.1134/S1607672924700960
D. A. Dibrov, A. S. Avdeeva, M. E. Diatroptov,  E. L. Nasonov
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Abstract

The objective of this study was to assess the level of antibodies to carbamylated proteins and analyze the clinical and immunological associations in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis.

. The study involved 150 patients with a reliable diagnosis of rheumatoid arthritis and 25 patients as healthy controls. Depending on ACPA values, two groups of patients were recruited: ACPA-positive (n = 75) and ACPA-negative (n = 75). RA activity was assessed by the DAS28 index. Determination of antibodies to carbamylated proteins was performed by enzyme-linked immunosorbent assay (BlueGene Biotech, China). Quantitative determination of ACPA in serum was performed by enzyme immunoassay using a commercial reagent kit (AxisShield, UK; upper limit of normal 5.0 U/mL; Orgentec, Germany; upper limit of normal 20.0 U/mL).

. Median anti-CarP in patients with RA was 126.2 [100.83; 157.41] ng/mL and was statistically significantly higher (p < 0.001) than in healthy controls (88.89 [70.53; 107.75] ng/mL). Among all patients with RA, 50 (33.3%) were anti-Carp-positive (22 (29.3%) in the ACPA(+) group and 28 (37.3%) in the ACPA(–) group), and one (2%) volunteer from healthy controls was anti-CarP(+) (p = 0.002). In ROC analysis performed to assess the diagnostic significance of anti-CarP for RA for all patients with RA, the area under the curve was 0.783 ± 0.047 with 95% CI: 0.691–0.874 (p < 0.001), with a cut-off point of 143 ng/mL, specificity 96%, sensitivity 36.7%.

In the ACPA(+) RA group, the erosion count was statistically significantly higher (p = 0.044) in anti-CarP(+) patients than in anti-CarP(–) patients. A weak direct correlation between anti-CarP and DAS28 was found in the ACPA(–) RA group.

. We studied the predictive value of anti-CarP as an auxiliary biomarker in ACPA(+) and ACPA(–) subtypes of RA. ACPA(+) anti-CarP(+) patients have a more “erosive” subtype of the disease than ACPA(+) anti-CarP(–) patients. In ACPA(–) patients, anti-CarP helps to identify a more erosive subtype of the disease, and among ACPA(–) patients it helps to reduce the proportion of seronegative patients. Further studies are required to determine the optimal standards for the laboratory diagnosis of anti-CarP and to clarify the diagnostic potential of these ABs as part of the differential diagnosis of arthritis in other rheumatic diseases.

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类风湿性关节炎 ACPA 阴性和 ACPA 阳性患者的抗卡巴米蛋白抗体。
本研究的目的是评估氨甲酰化蛋白抗体的水平,并分析 ACPA 阴性和 ACPA 阳性变异型类风湿性关节炎患者的临床和免疫学关联。研究涉及 150 名确诊为类风湿性关节炎的患者和 25 名健康对照组患者。根据 ACPA 值的不同,招募了两组患者:ACPA阳性(75人)和ACPA阴性(75人)。通过 DAS28 指数评估 RA 活性。氨甲酰化蛋白抗体的测定采用酶联免疫吸附试验(中国蓝基因生物技术有限公司)。血清中 ACPA 的定量检测采用酶联免疫法,使用商品试剂盒(AxisShield,英国;正常上限 5.0 U/mL;Orgentec,德国;正常上限 20.0 U/mL)。RA 患者抗 CarP 中位数为 126.2 [100.83; 157.41] ng/mL,在统计学上显著高于健康对照组(88.89 [70.53; 107.75] ng/mL)(p < 0.001)。在所有RA患者中,有50人(33.3%)抗Carp阳性(ACPA(+)组22人(29.3%),ACPA(-)组28人(37.3%)),健康对照组有1名志愿者(2%)抗CarP(+)(p = 0.002)。为评估抗 CarP 对所有 RA 患者的诊断意义而进行的 ROC 分析显示,曲线下面积为 0.783 ± 0.047,95% CI:0.691-0.874(p < 0.001),临界点为 143 ng/mL,特异性为 96%,敏感性为 36.7%。在ACPA(+)RA组中,抗CarP(+)患者的侵蚀计数在统计学上明显高于抗CarP(-)患者(p = 0.044)。在 ACPA(-)RA 组中,抗 CarP 与 DAS28 之间存在微弱的直接相关性。我们研究了抗 CarP 作为辅助生物标记物在 ACPA(+)和 ACPA(-)亚型 RA 中的预测价值。与ACPA(+)抗CarP(-)患者相比,ACPA(+)抗CarP(-)患者的疾病亚型更具 "侵蚀性"。在 ACPA(-)患者中,抗 CarP 有助于识别侵蚀性更强的疾病亚型,而在 ACPA(-)患者中,抗 CarP 有助于降低血清阴性患者的比例。还需要进一步研究来确定抗 CarP 实验室诊断的最佳标准,并明确这些 ABs 作为其他风湿性疾病关节炎鉴别诊断的一部分所具有的诊断潜力。
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来源期刊
Doklady Biochemistry and Biophysics
Doklady Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
1.60
自引率
12.50%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.
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