Brehm Victoria, Wang Ziyi, Rocha Luis, Jones Breanna, Jenq Robert R, Chang Chia-Chi, Cheng Guang-Shing, Hsu Joe, Sharifi Husham, Yanik Gregory, Luna Luis, Waqar Anum, Zaveri Jhankruti, Dickey Burton F, Bashoura Lara, Shpall Elizabeth J, Zinter Matt, O'Dwyer David, Champlin Richard E, Chen George, Alousi Amin, Paczesny Sophie, Peterson Christine B, Sheshadri Ajay
Department of Internal Medicine, Baylor College of Medicine, Houston, Texas.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Transplant Cell Ther. 2025 Sep;31(9):668.e1-668.e12. doi: 10.1016/j.jtct.2025.06.020. Epub 2025 Jun 19.
Bronchiolitis obliterans (BOS) is a manifestation of pulmonary chronic graft-versus-host disease (cGVHD) and is a devastating complication of allogeneic hematopoietic stem cell transplantation (HCT). Early detection and treatment of BOS may improve outcomes, but biomarkers that accurately identify BOS early are lacking. We aimed to determine whether certain validated cGVHD markers could also accurately diagnose BOS as compared with patients without BOS and with or without extrapulmonary cGVHD. In addition, we sought to determine whether dysbiosis of the gut or oral microbiomes was associated with BOS or with inflammatory biomarkers. We enrolled 43 recipients of allogeneic HCT, 16 of whom had BOS. For each patient, we obtained pulmonary function tests, measured the levels of 9 serum biomarkers utilizing enzyme-linked immunosorbent assays, and analyzed both the oral and gut microbiome using microbial DNA amplification and sequencing. We compared biomarker levels to lung function, both at baseline and over time, as well as to microbiome diversity. Higher IL1RL1 (P = .002) and IL-17 (P = .041) at enrollment were negatively correlated with FEV1% (forced expiratory volume in 1 second) lung function over time. Increases in IL1RL1 (P = .035), IL-17 (P = .009), and WFDC2 (P = .045) levels over time were associated with worsened lung function/FEV1% over time. There were minimal correlations between gut microbiome diversity and lung function or serum biomarkers. Oral microbiome alpha diversity was lower in subjects with BOS than without (P = .00057), and oral beta diversity was associated with FEV1% and with levels of several biomarkers. Our pilot study suggests that certain serum cGVHD markers may identify recipients of allogeneic HCT at higher risk for pulmonary impairment over time and that these markers should be followed with robust, controlled studies.
闭塞性细支气管炎（BOS）是肺部慢性移植物抗宿主病（cGVHD）的一种表现，是异基因造血干细胞移植（HCT）的一种严重并发症。BOS的早期检测和治疗可能会改善预后，但目前缺乏能够早期准确识别BOS的生物标志物。我们旨在确定某些经过验证的cGVHD标志物与无BOS以及有或无肺外cGVHD的患者相比，是否也能准确诊断BOS。此外，我们试图确定肠道或口腔微生物群的生态失调是否与BOS或炎症生物标志物相关。我们招募了43名异基因HCT受者，其中16人患有BOS。对于每位患者，我们进行了肺功能测试，采用酶联免疫吸附测定法测量了9种血清生物标志物的水平，并使用微生物DNA扩增和测序分析了口腔和肠道微生物群。我们将生物标志物水平与基线和随访期间的肺功能以及微生物群多样性进行了比较。入组时较高的IL1RL1（P = 0.002）和IL - 17（P = 0.041）与随访期间的1秒用力呼气容积（FEV1%）肺功能呈负相关。随着时间的推移，IL1RL1（P = 0.035）、IL - 17（P = 0.009）和WFDC2（P = 0.045）水平的升高与肺功能/FEV1%的恶化相关。肠道微生物群多样性与肺功能或血清生物标志物之间的相关性极小。患有BOS的受试者的口腔微生物群α多样性低于未患BOS的受试者（P = 0.00057），并且口腔β多样性与FEV1%以及几种生物标志物的水平相关。我们的初步研究表明，某些血清cGVHD标志物可能会识别出随着时间推移发生肺部损伤风险较高的异基因HCT受者，并且这些标志物应通过严格的对照研究进行跟踪。
