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Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation.

ABSTRACT: Pulmonary complications due to infection and idiopathic pneumonia syndrome (IPS), a noninfectious lung injury in hematopoietic stem cell transplant (HSCT) recipients, are frequent causes of transplantation-related mortality and morbidity. Our objective was to characterize the global bronchoalveolar lavage fluid (BALF) protein expression of IPS to identify proteins and pathways that differentiate IPS from infectious lung injury after HSCT. We studied 30 BALF samples from patients who developed lung injury within 180 days of HSCT or cellular therapy transfusion (natural killer cell transfusion). Adult subjects were classified as having IPS or infectious lung injury by the criteria outlined in the 2011 American Thoracic Society statement. BALF was depleted of hemoglobin and 14 high-abundance proteins, treated with trypsin, and labeled with isobaric tagging for relative and absolute quantification (iTRAQ) 8-plex reagent for two-dimensional capillary liquid chromatography (LC) and data dependent peptide tandem mass spectrometry (MS) on an Orbitrap Velos system in higher-energy collision-induced dissociation activation mode. Protein identification employed a target-decoy strategy using ProteinPilot within Galaxy P. The relative protein abundance was determined with reference to a global internal standard consisting of pooled BALF from patients with respiratory failure and no history of HSCT. A variance weighted t-test controlling for a false discovery rate of ?5% was used to identify proteins that showed differential expression between IPS and infectious lung injury. The biological relevance of these proteins was determined by using gene ontology enrichment analysis and Ingenuity Pathway Analysis. We characterized 12 IPS and 18 infectious lung injury BALF samples. In the 5 iTRAQ LC-MS/MS experiments 845, 735, 532, 615, and 594 proteins were identified for a total of 1125 unique proteins and 368 common proteins across all 5 LC-MS/MS experiments. When comparing IPS to infectious lung injury, 96 proteins were differentially expressed. Gene ontology enrichment analysis showed that these proteins participate in biological processes involved in the development of lung injury after HSCT. These include acute phase response signaling, complement system, coagulation system, liver X receptor (LXR)/retinoid X receptor (RXR), and farsenoid X receptor (FXR)/RXR modulation. We identified 2 canonical pathways modulated by TNF-?, FXR/RXR activation, and IL2 signaling in macrophages. The proteins also mapped to blood coagulation, fibrinolysis, and wound healing-processes that participate in organ repair. Cell movement was identified as significantly over-represented by proteins with differential expression between IPS and infection. In conclusion, the BALF protein expression in IPS differed significantly from infectious lung injury in HSCT recipients. These differences provide insights into mechanisms that are activated in lung injury in HSCT recipients and suggest potential therapeutic targets to augment lung repair.

SUBMITTER: Bhargava M

PROVIDER: S-EPMC4955710 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation.

Bhargava Maneesh M Viken Kevin J KJ Dey Sanjoy S Steinbach Michael S MS Wu Baolin B Jagtap Pratik D PD Higgins LeeAnn L Panoskaltsis-Mortari Angela A Weisdorf Daniel J DJ Kumar Vipin V Arora Mukta M Bitterman Peter B PB Ingbar David H DH Wendt Chris H CH

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20160505 8

Pulmonary complications due to infection and idiopathic pneumonia syndrome (IPS), a noninfectious lung injury in hematopoietic stem cell transplant (HSCT) recipients, are frequent causes of transplantation-related mortality and morbidity. Our objective was to characterize the global bronchoalveolar lavage fluid (BALF) protein expression of IPS to identify proteins and pathways that differentiate IPS from infectious lung injury after HSCT. We studied 30 BALF samples from patients who developed lu ...[more]

PMID: 27155584

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Project description:BackgroundBronchiolitis obliterans (BO) is one of the most common late non-infectious pulmonary complications after hematopoietic stem cell transplantation (HSCT). Lung transplantation (LT) is the only cure for patients with end-stage BO, but the overall efficacy is rarely reported. Our study aims to conclude and elucidate the clinical experience of our single center and provide a reference for the current selection of treatment.MethodsWe retrospectively analyzed the medical records of six patients with post-HSCT BO who received LT in our center from 2015 to 2019. The collected information included demographic data, surgery-related conditions, and postoperative follow-up data, which covered blood tests, infection status assessment, lung function assessment, anesthesia assessment, function assessment of other organs and so on. All patients were regularly followed up after discharge, which in the first year, was performed every 3 months. Over the next 2 years, patients were assessed every 6 months, and after 3 years, the frequency was once annually.ResultsThe mean age of patients at LT time was 28±13 years, with an interval of 72±48 months from HSCT. All patients developed hypercapnia with an average carbon dioxide partial pressure (pCO2) of 71.1±20.8 mmHg. Preoperative pulmonary function tests showed the mean actual forced expiratory volume in 1 second (FEV1) was 16.7%±5.9% of the predicted value in four patients. After assessment, four patients adopted sequential bilateral LT and two adopted right-sided LT. Due to hemodynamic instability, five patients adopted intraoperative assistance of extracorporeal membrane oxygenation (ECMO). One patient died of septic shock 9 days after surgery, and the other five survived healthy for 53±23 months. The actual value of FEV1 at 3 months postoperatively accounted for 57.9%±15.3% of the predicted value. No patients had recurrence of BO.ConclusionsLT may be a treatment worthy of consideration in patients with post-HSCT end-stage BO because it can improve lung function, quality of life and prolong survival of these selected patients.

Project description:Background and objectivesAKI is a major complication of allogeneic hematopoietic stem cell transplantation, increasing risk of nonrelapse mortality. AKI etiology is often ambiguous due to heterogeneity of conditioning/graft versus host disease regimens. To date, graft versus host disease and calcineurin inhibitor effects on AKI are not well defined. We aimed to describe AKI and assess pre-/post-hematopoietic transplant risk factors in a large recent cohort.Design, setting, participants, & measurementsWe performed a single-center, retrospective study of 616 allogeneic hematopoietic cell transplant recipients from 2014 to 2017. We defined AKI and CKD based on Kidney Disease Improving Global Outcomes (KDIGO) criteria and estimated GFR using the Chronic Kidney Disease Epidemiology Collaboration equation. We assessed AKI pre-/post-hematopoietic transplant risk factors using cause-specific Cox regression and association of AKI with CKD outcomes using chi-squared test. AKI was treated as a time-dependent variable in relation to nonrelapse mortality.ResultsIncidence of AKI by day 100 was 64%. Exposure to tacrolimus and other nephrotoxins conferred a higher risk of AKI, but tacrolimus levels were not associated with severity. Reduced-intensity conditioning carried higher AKI risk compared with myeloablative conditioning. Most stage 3 AKIs were due to ischemic acute tubular necrosis and calcineurin inhibitor nephrotoxicity. KRT was initiated in 21 out of 616 patients (3%); of these 21 patients, nine (43%) recovered and five (24%) survived to hospital discharge. T cell-depleted transplants, higher baseline serum albumin, and non-Hispanic ethnicity were associated with lower risk of AKI. CKD developed in 21% (73 of 345) of patients after 12 months. Nonrelapse mortality was higher in those with AKI (hazard ratio, 2.77; 95% confidence interval, 1.8 to 4.27).ConclusionsAKI post-hematopoietic cell transplant remains a major concern. Risk of AKI was higher with exposure to calcineurin inhibitors. T cell-depleted hematopoietic cell transplants and higher serum albumin had lower risk of AKI. Of the patients requiring KRT, 43% recovered kidney function.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_09_07_CJN19801220.mp3.

Dataset Information

Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation.

Publications

Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation.

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