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抗酸分枝杆菌糖脂抗体作为鸟分枝杆菌胞内复合体肺病的生物标志物与长期预后的关系。

Long-Term Prognosis and Antimycobacterial Glycolipid Antibody as Biomarker in Mycobacterium avium-intracellulare Complex Pulmonary Disease.

机构信息

Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Japan.

Graduate School of Medical Safety Management, Jikei University of Health Care Sciences, Osaka, Japan.

出版信息

Microbiol Spectr. 2022 Jun 29;10(3):e0053022. doi: 10.1128/spectrum.00530-22. Epub 2022 Apr 25.

Abstract

Clinical characteristics and outcomes of multidrug chemotherapy have been used as the main prognostic factors for Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) over the last decade; however, no useful prognostic biomarkers have been reported. The aim is to ascertain whether the serum antibody titers could include useful prognostic predictors of MAC-PD. Ninety-four patients with MAC-PD were enrolled and regularly followed up with for more than 5 years or until death. Cox proportional hazard regression and receiver operating characteristic (ROC) curve analyses were used to identify predictors of mortality in this prospective observational study. According to treatment outcomes, 85 patients completed follow-up and were classified into four groups. Seventeen patients (20%) died during follow-up (median, 10.1 years; interquartile range, 8.1 to 12.4 years). All 11 patients with MAC-PD-specific death were included in the 14 patients of the group nonresponsive to the multidrug chemotherapy. They had significantly higher anti- glycolipid (MBGL) antibody titers than those in the other groups and a significantly ( < 0.0001) poorer survival prognosis. The anti-MBGL antibody titers also served as a negative prognostic factor. A cutoff score of 7, which was calculated by clinical poor prognostic characteristics and anti-MBGL antibody titers, differentiated the nonresponse group and the other groups at baseline (sensitivity, specificity, and area under the curve: 92.9%, 81.7%, and 0.95, respectively). In conclusion, anti-MBGL antibody titers were useful to assess the refractory MAC-PD. The predictions of treatment outcome and mortality become more accurate by using anti-MBGL antibody and clinical poor prognostic characteristics together. The natural history of MAC-PD is challenging to predict in immunocompetent patients at diagnosis, and the current multidrug chemotherapy options are not strong enough to eliminate mycobacteria from the lungs. Therefore, the diagnosis of MAC-PD does not necessarily lead to the decision to start chemotherapy. We have also observed refractory patients in clinical practice, who were resistant to multiple-drug chemotherapy and showed persistent excretion of MAC bacilli and progressive worsening of chest radiographic findings until death. We have reported that the measurements of anti-MBGL antibody titers helped assess refractory MAC-PD in this study. Furthermore, the predictions of treatment outcome and mortality become more accurate by using the anti-MBGL antibody in addition to clinical poor prognostic characteristics, which were older age, lower body mass index, the positive results of a smear test for acid-fast bacteria (AFB), and presence of cavitary disease.

摘要

在过去的十年中,抗多种药物化疗的临床特征和结果已被用作分枝杆菌肺病(MAC-PD)的主要预后因素;然而,尚未报道有用的预后生物标志物。本研究旨在确定血清抗体滴度是否可以包含 MAC-PD 的有用预后预测因子。

纳入了 94 例 MAC-PD 患者,并对其进行了超过 5 年的定期随访或直至死亡。在这项前瞻性观察研究中,使用 Cox 比例风险回归和受试者工作特征(ROC)曲线分析来确定死亡率的预测因子。根据治疗结果,85 例患者完成了随访,并分为四组。在随访期间,有 17 例患者(20%)死亡(中位数为 10.1 年;四分位间距为 8.1 至 12.4 年)。MAC-PD 特异性死亡的 11 例患者均包含在对多药化疗无反应的 14 例患者中。他们的抗糖脂(MBGL)抗体滴度明显高于其他组,且生存预后明显(<0.0001)较差。抗-MBGL 抗体滴度也是一个负预后因素。通过临床不良预后特征和抗-MBGL 抗体滴度计算出的 7 分为截距评分,可在基线时区分无反应组和其他组(敏感性、特异性和曲线下面积分别为 92.9%、81.7%和 0.95)。

总之,抗-MBGL 抗体滴度可用于评估难治性 MAC-PD。通过同时使用抗-MBGL 抗体和临床不良预后特征,治疗结果和死亡率的预测会更加准确。在免疫功能正常的患者中,MAC-PD 的自然史很难预测,目前的多药化疗方案还不够强大,无法从肺部消除分枝杆菌。因此,MAC-PD 的诊断并不一定导致开始化疗的决定。我们在临床实践中也观察到了耐药患者,他们对多种药物化疗耐药,持续排出 MAC 杆菌,并出现胸部 X 线表现恶化,直至死亡。我们曾报道,在这项研究中,抗-MBGL 抗体滴度的测量有助于评估难治性 MAC-PD。此外,通过同时使用抗-MBGL 抗体和临床不良预后特征(年龄较大、体重指数较低、抗酸杆菌涂片阳性结果和存在空洞性疾病),治疗结果和死亡率的预测会更加准确。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2637/9241601/863dc811608d/spectrum.00530-22-f001.jpg

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