Biology Department, Abilene Christian University, Abilene, Texas, United States of America.
PZM Diagnostics, Charleston, West Virginia, United States of America.
PLoS One. 2024 Oct 4;19(10):e0308911. doi: 10.1371/journal.pone.0308911. eCollection 2024.
Increasing evidence links a worldwide bacterial infection of cattle and other animal species by Mycobacterium avium ssp. paratuberculosis (MAP) to Crohn's disease (CD). A large, FDA phase 2/3 controlled clinical trial of combination antimycobacterial antibiotic therapy for CD has been completed, and the report describing the trial is pending publication. The identification of MAP infection in CD patients will become increasingly important. Thus, it is desirable to develop MAP-based tests that accurately predict which CD patients have a MAP infection. A prospective, case-control laboratory test study of 199 subjects (61 CD patients and 138 non-CD controls) was performed using a panel of MAP antigens, including Hsp65, PknG, PtpA, CL1, and MAP IDEXX, which were measured under blind conditions in the plasma of the 199 subjects. Results showed that compared to any individual MAP antigen, combinations of antigens showed improved CD classification performance. For the Hsp65 antigen, the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), correct classification (CC), and area under the curve (AUC) were 59.02%, 58.70%, 38.71%, 76.42%, 59.3% and 0.606, respectively. For the best combination of MAP antibodies (Hsp65 and PknG), the SEN, SPE, PPV, NPV, CC, and AUC were 59.02%, 60.87%, 40.00%, 77.06%, 60.30%, and 0.631, respectively. Further improvement of the CD classification performance was achieved by combining IFN-γ, IL-8, and IL-17 cytokines with antibodies against MAP antigens, yielding SEN, SPE, PPV, NPV, CC, and AUC of 62.3%, 62.32%, 42.22%, 78.9%, 62.31% and 0.708, respectively. Thus, combinations of antibodies against MAP antigens and cytokine levels yield better CD diagnostic predictive performance than any individual antibodies against MAP antigens.
越来越多的证据表明，牛和其他动物物种的分枝杆菌感染与分枝杆菌副结核亚种（MAP）与克罗恩病（CD）有关。一项大型的 FDA 二期/三期对照临床试验已经完成了针对 CD 的联合抗分枝杆菌抗生素治疗，报告正在等待发表。在 CD 患者中识别 MAP 感染将变得越来越重要。因此，开发能够准确预测哪些 CD 患者存在 MAP 感染的 MAP 检测方法是非常有必要的。在这项前瞻性病例对照实验室检测研究中，使用了一组 MAP 抗原，包括 Hsp65、PknG、PtpA、CL1 和 MAP IDEXX，对 199 名受试者（61 名 CD 患者和 138 名非 CD 对照组）的血浆进行了盲法检测。结果表明，与任何单个 MAP 抗原相比，抗原组合显示出改善的 CD 分类性能。对于 Hsp65 抗原，敏感性（SEN）、特异性（SPE）、阳性预测值（PPV）、阴性预测值（NPV）、正确分类（CC）和曲线下面积（AUC）分别为 59.02%、58.70%、38.71%、76.42%、59.3%和 0.606。对于 MAP 抗体（Hsp65 和 PknG）的最佳组合，SEN、SPE、PPV、NPV、CC 和 AUC 分别为 59.02%、60.87%、40.00%、77.06%、60.30%和 0.631。通过将 IFN-γ、IL-8 和 IL-17 细胞因子与 MAP 抗原抗体结合，进一步提高了 CD 的分类性能，得到了 SEN、SPE、PPV、NPV、CC 和 AUC 分别为 62.3%、62.32%、42.22%、78.9%、62.31%和 0.708。因此，MAP 抗原抗体和细胞因子水平的组合比任何单个 MAP 抗原抗体的 CD 诊断预测性能都要好。
