Lack of association of platelet-derived growth factor (PDGF) receptor autoantibodies and severity of chronic graft-versus-host disease (GvHD)

Spies-Weisshart, Baerbel; Schilling, K; Böhmer, Frank D.; Hochhaus, Andreas; Sayer, Herbert G.; Scholl, Sebastian

doi:10.1007/s00432-013-1451-z

Cited by 10 publications

(11 citation statements)

References 30 publications

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“…Moreover, the frequent production of auto-antibodies by patients with chronic GVHD suggests that loss of B-cell tolerance is operative (230). While a number of auto-antibodies, including Anti-Nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), and platelet-derived growth factor receptor alpha (PDGFRα), have been found in association with chronic GVHD (231–234), these findings have been variable. An exception is antibodies directed against Y-chromosome encoded epitopes (H-Y antibodies) in male recipients of stem cell grafts from female donors who develop chronic GVHD (224, 225, 235).…”

Section: A Three Phase Model For Chronic Gvhd Biologymentioning

confidence: 99%

The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

Cooke

Luznik

Sarantopoulos

et al. 2017

Biology of Blood and Marrow Transplantation

360

322

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Summary Chronic graft-versus-host disease (GVHD) is the leading cause of late, non-relapse, mortality and disability in allogeneic hematopoietic cell transplantation (HCT) patients and a major obstacle to improving outcomes. Chronic GVHD biology remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies. The goals of this task force review are as follows: Summarize the current “state-of-the-science” regarding pathogenic mechanisms of chronic GVHD and critical knowledge gaps.Develop working hypotheses/overriding concepts for chronic GVHD development.Define the usefulness of current preclinical models to test working hypotheses and ultimately discover and develop new therapeutic strategies.Identify shortcomings of preclinical models, and define criteria for the creation of additional models to address these limitations. This document is intended as a review of our understanding of chronic GVHD biology and therapies resulting from preclinical studies, and as a platform for developing innovative clinical strategies to prevent and treat chronic GVHD.

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Section: A Three Phase Model For Chronic Gvhd Biologymentioning

confidence: 99%

The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

Cooke

Luznik

Sarantopoulos

et al. 2017

Biology of Blood and Marrow Transplantation

360

322

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“…The presence of these receptor autoantibodies in scleroderma is not fully established as one study demonstrated the existence of these autoantibodies in the disease, however, another study failed to replicate this finding [7,24]. In addition, a recent study on the presence of PDGFR antibodies in patients with chronic GVHD failed to show an association between autoantibody levels and disease severity [90]. …”

Section: The Role Of Nox In Skin Fibrosismentioning

confidence: 99%

NADPH oxidase enzymes in skin fibrosis: molecular targets and therapeutic agents

et al. 2013

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Fibrosis is characterized by the excessive deposition of extracellular matrix components eventually resulting in organ dysfunction and failure. In dermatology, fibrosis is the hallmark component of many skin diseases, including systemic sclerosis, graft versus host disease, hypertrophic scars, keloids, nephrogenic systemic fibrosis, porphyria cutanea tarda, restrictive dermopathy and other conditions. Fibrotic skin disorders may be debilitating and impair quality of life. There are few FDA-approved anti-fibrotic drugs; thus, research in this area is crucial in addressing this deficiency. Recent investigations elucidating the pathogenesis of skin fibrosis have implicated endogenous reactive oxygen species produced by the multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzyme complex. In this review we discuss Nox enzymes and their role in skin fibrosis. An overview of the Nox enzyme family is presented and their role in the pathogenesis of skin fibrosis is discussed. The mechanisms that Nox enzymes influence specific skin fibrotic disorders are also reviewed. Finally, we describe the therapeutic approaches to ameliorate skin fibrosis by directly targeting Nox enzymes with the use of statins, p47phox subunit modulators, or GKT137831, a competitive inhibitor of Nox enzymes. Nox enzymes can also be targeted indirectly via scavenging ROS with antioxidants. We believe that Nox modulators are worthy of further investigation and have the potential to transform the management of skin fibrosis by dermatologists.

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“…However, in spite of evidence of their frequent detection in patients, the biological significance and role of autoantibodies in cGVHD is not defined [33]. The 2005 NIH consensus project provided new classification of cGVHD diagnosis and staging [2,34].…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of autoantibodies in a large cohort of patients with chronic graft‐versus‐host disease defined by NIH criteria

et al. 2014

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There is an unmet need for identifying new clinical biomarkers in chronic Graft-versus-Host-disease (cGVHD) suitable for diagnosis and disease monitoring. Circulating autoantibodies represent an ongoing immune response and suggest a pathogenic role for B cells in cGVHD. Autoantibodies could be useful markers of cGVHD disease activity, severity, or organ specificity; however, their clinical utility is not established. The focus of this study was to determine the incidence and associations of a broad array of clinical autoantibodies with cGVHD manifestations in a large patient cohort characterized by NIH criteria. A panel of 21 circulating antibodies commonly used in clinical medicine was tested in 280 cGVHD patients (70% severe) enrolled in a cross-sectional prospective natural history study. Median cGVHD duration was two years. Patients with circulating autoantibodies (62%) had significantly higher levels of IgM (P < 0.0001), IgG (P < 0.0001), and IgA (P = 0.001), elevated uric acid (P = 0.008) and total protein (P = 0.0004), and higher numbers of CD31 (P = 0.002), CD41 (P = 0.001), CD81 (P = 0.023) T cells, and CD191 B cells (P < 0.0001). Multiple antibodies were detected in 35% of patients. Prior rituximab therapy (n = 66) was associated with reduced presence of autoantibodies (48 vs. 66% P = 0.01). Only oral cGVHD was significantly associated with presence of autoantibodies in this study (P = 0.028). No significant associations were found between cGVHD activity and severity, and presence of autoantibodies. Circulating autoantibodies are common in patients with advanced cGVHD. Their presence is associated with better quantitative immunologic reconstitution but does not have utility as a clinical biomarker of cGVHD.

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Lack of association of platelet-derived growth factor (PDGF) receptor autoantibodies and severity of chronic graft-versus-host disease (GvHD)

Abstract: Platelet-derived growth factor receptor autoantibodies could easily be detected in patient sera. Nevertheless, we did not observe any correlation between the presence of PDGF receptor autoantibodies and the severity of chronic GvHD in patients who underwent allogeneic PBSCT.

Cited by 10 publications

References 30 publications

The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

NADPH oxidase enzymes in skin fibrosis: molecular targets and therapeutic agents

Clinical significance of autoantibodies in a large cohort of patients with chronic graft‐versus‐host disease defined by NIH criteria

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