Differential Cytokine, Chemokine and Growth Factor Expression in Phenotypes of Chronic Lung Allograft Dysfunction

Verleden, Stijn E.; Ruttens, David; Vos, Robin; Vandermeulen, Elly; Moelants, Eva; Mortier, Anneleen; Raemdonck, Dirk Van; Proost, Paul; Schols, Dominique; Verleden, Geert M.; Vanaudenaerde, Bart M.

doi:10.1097/tp.0000000000000269

Cited by 59 publications

(55 citation statements)

References 21 publications

(21 reference statements)

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“…The presence of HLA antibodies seems to be more associated with rCLAD compared to BOS which is in line with the hypothesis of (at least part) overlap (65). Of interest is also that in BAL, VEGF levels are decreased in rCLAD patients (34), which is in line with the hypothesis that the capillary network is of importance, which was also demonstrated in a descriptive pathological study (66). In contrast, the lymphatics do not seem to be altered in rCLAD, which is surprising given the predominant distribution (pleural and septal) of fibrosis in rCLAD (67).…”

Section: Risk Factors and Mechanismssupporting

confidence: 71%

“…In fact, a recent BAL cytokine and chemokine analysis, could not detect any molecule that was differentially regulated between stable (non-rejecting) patients and patients with BOS (34). Consequently, some groups have tried to identify blood markers blood for BOS development, but so far none have proven to be very sensitive and specific.…”

Section: Risk Factors and Mechanisms Of Bosmentioning

confidence: 99%

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Chronic lung allograft dysfunction phenotypes and treatment

et al. 2017

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CT and obliterative bronchiolitis (OB) on histopathology, while RAS/rCLAD patients show a restrictive pulmonary function, persistent pleuro-parenchymal infiltrates on CT and pleuroparenchymal fibro-elastosis on biopsies. Importantly, the patients with RAS/rCLAD have a severely limited survival post diagnosis of 6-18 months compared to 3-5 years after BOS diagnosis. In this review, we will review historical evidence for this heterogeneity and we will highlight the clinical, radiological, histopathological characteristics of both phenotypes, as well as their risk factors. Treatment of CLAD remains troublesome, nevertheless, we will give an overview of different treatment strategies that have been tried with some success. Adequate phenotyping remains difficult but is clearly needed for both clinical and scientific purposes.

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Section: Risk Factors and Mechanismssupporting

confidence: 71%

Section: Risk Factors and Mechanisms Of Bosmentioning

confidence: 99%

Chronic lung allograft dysfunction phenotypes and treatment

et al. 2017

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“…It was also found that after liver transplantation in patients with recurrent hepatitis plasma CXCL-10 could differentiate patients with slow from those with rapid progression of fibrosis 50 . Moreover, in a biomarker discovery study in lung transplant patients, CXCL-8, CXCL-10, CCL-2, CCL-3, CCL-4 CCL-7, and CCL-3 in bronchial lavage fluid could differentiate between different phenotypes of chronic lung allograft dysfuntion 51 . A few clinical targeted proteomics/protein biomarker studies in heart transplant patients have also been described (for a review, please see reference 9 ).…”

Section: Predictive Biomarkers In Transplantation Based On Targeted Pmentioning

confidence: 99%

Biomarkers in Transplantation—Proteomics and Metabolomics

Christians

Klawitter

2016

Therapeutic Drug Monitoring

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Modern multi-analyte “omics” technologies allow for the identification of molecular signatures that confer significantly more information than measurement of a single parameter as typically used in current medical diagnostics. Proteomics and metabolomics bioanalytical assays capture a large set of proteins and metabolites in body fluids, cells or tissues and, complementing genomics, assess the phenome. Proteomics and metabolomics contribute to the development of novel predictive clinical biomarkers in transplantation in two ways: They can be used to generate a diagnostic fingerprint or they can be used to discover individual proteins and metabolites of diagnostic potential. Much fewer metabolomics than proteomics biomarker studies in transplant patients have been reported and, in contrast to proteomics discovery studies, new lead metabolite markers have yet to emerge. Most clinical proteomics studies have been discovery studies. Several of these studies have assessed diagnostic sensitivity and specificity. Nevertheless, none of these newly discovered protein biomarkers has yet been implemented in clinical decision making in transplantation. The currently most advanced markers discovered in proteomics studies in transplant patients are the chemokines CXCL-9 and CXCL-10, which have successfully been validated in larger multi-center trials in kidney transplant patients. These chemokines can be measured using standard immunoassay platforms, which should facilitate clinical implementation. Based on the published evidence, it is reasonable to expect that these chemokine markers can help guiding and individualizing immunosuppressive regimens, may be able to predict acute and chronic T cell and anti-body mediated rejection and may be useful tools for risk stratification of kidney transplant patients.

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“…Compared with the much better known BOS clinical phenotype, patients with RAS experience a worse prognosis (3.5 versus 1.5 years); the reasons for this difference in prognosis are poorly understood [7]. Patients affected by RAS appear to progress in a more stepwise pattern [8], that might be driven by intermittent up-regulation of pro-inflammatory mediators [9,10] during episodes of diffuse alveolar damage [11,12] similar to those observed in patients with idiopathic pulmonary fibrosis (IPF).…”

Section: Introductionmentioning

confidence: 99%

Linking clinical phenotypes of chronic lung allograft dysfunction to changes in lung structure

et al. 2015

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Chronic lung allograft dysfunction (CLAD) remains the major barrier to long-term success after lung transplantation. This report compares gross and microscopic features of lungs removed from patients receiving a redo-transplant as treatment for CLAD.Lungs donated by patients with either the bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) phenotype of CLAD and appropriate control lungs (eight per group) were airinflated, frozen solid and kept frozen while a multi-detector computed tomography (MDCT) was obtained. The lung was then cut into 2-cm thick transverse slices and sampled for micro-CT and histopathology.The MDCT showed reduced lung volume with increased lung weight and density in RAS versus BOS and control ( p<0.05). Although pre-terminal bronchioles were obstructed in both phenotypes, RAS lungs showed a reduction of pre-terminal bronchioles ( p<0.01). Micro-CT and matched histopathology showed that RAS was associated with reduced numbers of terminal bronchioles/lung compared to BOS and controls ( p<0.01), with expansion of the interstitial compartment and obliteration of the alveolar airspaces by fibrous connective tissue.RAS is associated with greater destruction of both pre-terminal and terminal bronchioles. Additionally, the interstitial compartments are expanded and alveolar airspaces are obliterated by accumulation of fibrous connective tissue. @ERSpublications Restrictive allograft syndrome is associated with greater destruction of both pre-terminal and terminal bronchioles

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Differential Cytokine, Chemokine and Growth Factor Expression in Phenotypes of Chronic Lung Allograft Dysfunction

Abstract: There were major differences in cytokine and chemokine expression in our different study groups. Especially IL-6, but also IP-10/CXCL10, and VEGF may be interesting mediators in RAS.

Cited by 59 publications

References 21 publications

Chronic lung allograft dysfunction phenotypes and treatment

Chronic lung allograft dysfunction phenotypes and treatment

Biomarkers in Transplantation—Proteomics and Metabolomics

Linking clinical phenotypes of chronic lung allograft dysfunction to changes in lung structure

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