Journal of Cystic Fibrosis ( IF 5.2 ) Pub Date : 2021-09-10 , DOI: 10.1016/j.jcf.2021.08.019 Vincent Le Moigne 1 , Anne-Laure Roux 2 , Hélène Mahoudo 1 , Gaëtan Christien 1 , Agnès Ferroni 3 , Oana Dumitrescu 4 , Gérard Lina 4 , Jean-Philippe Bouchara 5 , Patrick Plésiat 6 , Jean-Louis Gaillard 2 , Stéphane Canaan 7 , Geneviève Héry-Arnaud 8 , Jean-Louis Herrmann 9
Background
Culture conditions sometimes make it difficult to detect non-tuberculous mycobacteria (NTM), particularly Mycobacterium abscessus, an emerging cystic fibrosis (CF) pathogen. The diagnosis of NTM positive cases not detected by classical culture methods might benefit from the development of a serological assay.
Methods
As part of a diagnostic accuracy study, a total of 173 sera CF-patients, including 33 patients with M. abscessus positive cultures, and 31 non-CF healthy controls (HC) were evaluated. Four M. abscessus antigens were used separately, comprising two surface extracts (Interphase (INP) and a TLR2 positive extract (TLR2eF)) and two recombinant proteins (rMAB_2545c and rMAB_0555 also known as the phospholipase C (rPLC)).
Results
TLR2eF and rPLC were the most efficient antigens to discriminate NTM-culture positive CF-patients from NTM-culture negative CF-patients. The best clinical values were obtained for the detection of M. abscessus-culture positive CF-patients; with sensitivities for the TLR2eF and rPLC of 81.2% (95% CI:65.7–92.3%) and 87.9% (95% CI:71.9–95.6%) respectively, and specificities of 88.9% (95% CI:85.3–94.8%) and 84.8% (95% CI:80.6–91.5%) respectively. When considering as positive all sera, giving a positive response in at least one of the two tests, and, as negative, all sera negative for both tests, we obtained a sensitivity of 93.9% and a specificity of 80.7% for the detection of M. abscessus-culture positive CF-patients.
Conclusion
High antibody titers against TLR2eF and rPLC were obtained in M. abscessus-culture positive CF-patients, allowing us to consider these serological markers as potential tools in the detection of CF-patients infected with M. abscessus.
中文翻译:
用于诊断囊性纤维化患者脓肿分枝杆菌感染的血清学生物标志物
背景
培养条件有时难以检测非结核分枝杆菌 (NTM),特别是脓肿分枝杆菌,一种新出现的囊性纤维化 (CF) 病原体。传统培养方法未检测到的 NTM 阳性病例的诊断可能受益于血清学检测的发展。
方法
作为诊断准确性研究的一部分,共评估了 173 名血清 CF 患者,包括 33 名脓肿分枝杆菌阳性培养患者和 31 名非 CF 健康对照 (HC)。分别使用了四种脓肿分枝杆菌抗原,包括两种表面提取物(间期 (INP) 和 TLR2 阳性提取物 (TLR2eF))和两种重组蛋白(rMAB_2545c 和 rMAB_0555,也称为磷脂酶 C (rPLC))。
结果
TLR2eF 和 rPLC 是区分 NTM 培养阳性 CF 患者和 NTM 培养阴性 CF 患者的最有效抗原。对于脓肿分枝杆菌培养阳性的CF患者的检测,获得了最佳的临床价值;对 TLR2eF 和 rPLC 的敏感性分别为 81.2% (95% CI:65.7–92.3%) 和 87.9% (95% CI:71.9–95.6%),特异性为 88.9% (95% CI:85.3–94.8%)和 84.8% (95% CI:80.6–91.5%)。当将所有血清视为阳性时,至少在两项测试中的一项中给出阳性反应,并且在两项测试中所有血清均为阴性时,我们获得了 93.9% 的灵敏度和 80.7% 的特异性检测M . 脓肿培养阳性 CF 患者。
结论
在脓肿分枝杆菌培养阳性 CF 患者中获得了针对 TLR2eF 和 rPLC 的高抗体滴度,这使我们能够将这些血清学标志物视为检测感染脓肿分枝杆菌的 CF 患者的潜在工具。