Blood proteomics of paediatric bronchiolitis obliterans syndrome after haematopoietic cell transplant

<h4>Background</h4>The molecular determinants for lung graft-<i>versus</i>-host disease-associated bronchiolitis obliterans syndrome (BOS) are poorly understood, and biomarkers in children following haematopoietic stem cell transplant do not exist. To address this gap, we analysed plasma samples from 21 paediatric stem cell transplant recipients prior to and at diagnosis of BOS.<h4>Methods</h4>Participants included three cohorts: seven with BOS; seven sex-, age- and timepoint-matched with severe graft-<i>versus</i>-host disease alone; and seven sex-, age- and timepoint-matched transplant recipients without BOS or other graft-<i>versus</i>-host disease.<h4>Results</h4>Our proteomic approach evaluated the expression of 190-12 588 protein isoforms, depending on statistical stringency, and distinguished the three cohorts of paediatric patients prior to and at the time of BOS diagnosis. Differences included proteins that regulate chromatin modification, acute phase signalling, complement, fibrosis, hypoxia, serine protease inhibition, vitamin transport, glucocorticoid receptor transactivation and blood coagulation pathways. A subset of newly discovered proteins was cross-platform validated by ELISA in a larger cohort of paediatric patients 14 (n=107), 30 (n=108), 60 (n=108) and 100 (n=134) days post-transplant. Pathways analysis highlighted potential therapeutics including azithromycin, statins, pazopanib and cediranib.<h4>Conclusion</h4>Our strategy offers a potential for early diagnosis and the identification of interventions for paediatric stem cell transplant-associated graft-<i>versus</i>-host disease and BOS.