University of Pennsylvania, Philadelphia.
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Arthritis Rheumatol. 2021 Sep;73(9):1703-1712. doi: 10.1002/art.41723. Epub 2021 Jul 31.
Little is known about temporal changes in nasal bacteria in granulomatosis with polyangiitis (GPA). This study was undertaken to examine longitudinal changes in the nasal microbiome in association with relapse in GPA patients.
Bacterial 16S ribosomal RNA gene sequencing was performed on nasal swabs from 19 patients with GPA who were followed up longitudinally for a total of 78 visits, including 9 patients who experienced a relapse and 10 patients who remained in remission. Relative abundance of bacteria and ratios between bacteria were examined. Generalized estimating equation models were used to evaluate the association between bacterial composition and 1) disease activity and 2) levels of antineutrophil cytoplasmic antibody (ANCA) with specificity for proteinase 3 (PR3), adjusted for medication.
Corynebacterium and Staphylococcus were the most abundant bacterial genera across all nasal samples. Patients with quiescent disease maintained a stable ratio of Corynebacterium to Staphylococcus across visits. In contrast, in patients who experienced a relapse, a significantly lower ratio was observed at the visit prior to relapse, followed by a higher ratio at the time of relapse (adjusted P < 0.01). Species-level analysis identified an association between a higher abundance of nasal Corynebacterium tuberculostearicum and 1) relapse (adjusted P = 0.04) and 2) higher PR3-ANCA levels (adjusted P = 0.02).
In GPA, significant changes occur in the nasal microbiome over time and are associated with disease activity. The occurrence of these changes months prior to the onset of relapse supports a pathogenic role of nasal bacteria in GPA. Our results uphold existing hypotheses implicating Staphylococcus as an instigator of disease and have generated a novel finding involving Corynebacterium as a potential mediator of disease in GPA.
关于肉芽肿性多血管炎（GPA）患者鼻部细菌的时间变化知之甚少。本研究旨在检查 GPA 患者中与疾病复发相关的鼻腔微生物组的纵向变化。
对 19 例 GPA 患者的鼻腔拭子进行了细菌 16S 核糖体 RNA 基因测序，这些患者进行了纵向随访，总共进行了 78 次就诊，其中 9 例患者复发，10 例患者缓解。检查了细菌的相对丰度和细菌之间的比例。使用广义估计方程模型评估细菌组成与 1）疾病活动度和 2）抗中性粒细胞胞质抗体（针对蛋白酶 3 的特异性 PR3-ANCA）水平之间的关联，同时调整了药物因素。
在所有鼻腔样本中，棒状杆菌和葡萄球菌是最丰富的细菌属。处于疾病缓解期的患者在整个就诊过程中保持着稳定的棒状杆菌与葡萄球菌比值。相比之下，在经历复发的患者中，在复发前就诊时观察到比值显著降低，随后在复发时比值升高（调整后 P <0.01）。种水平分析发现，鼻腔结核棒状杆菌的丰度与 1）复发（调整后 P = 0.04）和 2）PR3-ANCA 水平升高（调整后 P = 0.02）相关。
在 GPA 中，鼻腔微生物组随时间发生显著变化，并与疾病活动度相关。这些变化在复发前数月发生，支持鼻腔细菌在 GPA 中的致病作用。我们的结果支持了现有的假说，即葡萄球菌是疾病的引发因素，并提出了一个新的发现，即棒状杆菌可能是 GPA 疾病的潜在介质。
