Tumour necrosis factor receptor type II 196M/R genotype correlates with circulating soluble receptor levels in normal subjects and with graft-versus-host disease after sibling allogeneic bone marrow transplantation1

Stark, G; Dickinson, Anne M.; Jackson, Graham; Taylor, Pennie; Proctor, Stephen J.; Middleton, Peter G.

doi:10.1097/01.tp.0000092496.05951.d5

Cited by 57 publications

(40 citation statements)

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“…A polymorphism (196 R/M) in the TNF receptor II gene in HLA-matched unrelated HSCT found that recipients of TNFRII-196R-positive donors had a higher incidence of severe GvHD and a lower rate of relapse than from TNFRII 196 M homozygous donors (Ishikawa et al, 2002). The recipient TNFRII 196R allele was associated with acute GvHD incidence but the TNFRII 196RR genotype in the donor was associated with (increased) incidence of extensive chronic GvHD in an HLA-matched sibling HSCT cohort (Stark et al, 2003).…”

Section: Tnf Genesmentioning

confidence: 98%

“…now been associated with GvHD and HSCT transplant outcomes (Brok et al, 1998;Fishman et al, 1998;Middleton et al, 1998;Cavet et al, 1999Cavet et al, , 2001Grainger et al, 1999;Cullup et al, 2001Cullup et al, , 2003Socié et al, 2001;Hattori et al, 2002;Ishikawa et al, 2002;Kögler et al, 2002;Rocha et al, 2002;Lin et al, 2003;MacMillan et al, 2003a;Stark et al, 2003;Keen et al, 2004).…”

Section: Il-10mentioning

confidence: 99%

“…Severe toxic complications (Bogunia-Kubik et al, 2003) TNF receptor Unknown Incidence of acute GvHD HLA-matched siblings HSCT (Stark et al, 2003) More severe GvHD in HLA matched unrelated donor HSCT (Ishikawa et al, 2002) TNFRII 196R…”

Section: Tnfd3mentioning

confidence: 99%

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Genetic polymorphisms predicting the outcome of bone marrow transplants

et al. 2004

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SummaryAnalysis of non‐histocompatibility leucocyte antigen (HLA) functional genomics, together with conventional risk factors in haematopoietic stem cell transplantation (HSCT) can lead to predicting outcome in HLA‐matched sibling transplant recipients. Polymorphisms of cytokine genes including tumour necrosis factor α, interleukin‐10, interferon γ and interleukin (IL)‐6, associate with more severe acute graft‐versus‐host disease (aGvHD). Donor genotype for IL‐1 receptor antagonist (IL‐1Ra) has been associated with reduced aGvHD severity. Other genotypes (patient IL‐1Ra, IL‐6 and donor IL‐1α) have been associated with chronic GvHD, or overall survival (Vitamin D receptor and oestrogen receptor). Polymorphisms within genes associated with host defence/inflammatory responses (mannose binding lectin genes, myeloperoxidase genes and the FCγ receptors) have been associated with infections. Polymorphisms of pharmacogenes, such as methylenetetrahydrofolate‐reductase, have been associated with aGvHD and other post‐transplant complications. The NOD2 gene polymorphism, associated with Crohn's disease, has been shown to be associated with risk of gut GvHD. The majority of the studies have been carried out in single centre HLA‐matched sibling cohorts and in relatively few matched unrelated donor transplants. This review gives an overall perspective of the current field of non‐HLA genetics with regard to HSCT outcome, clinical relevance and potential application of the results to clinical management of HSCT.

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Section: Tnf Genesmentioning

confidence: 98%

Section: Il-10mentioning

confidence: 99%

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Genetic polymorphisms predicting the outcome of bone marrow transplants

et al. 2004

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“…88 Recipient IL-1Ra polymorphisms associated with lower production of IL-1Ra, and thus perhaps more biologic activity of IL-1 were also associated with chronic GVHD. 86 Recipient IL-6 polymorphisms have been associated with chronic GVHD in 2 reports, 89,90 though these studies failed to find an association with other donor or recipient polymorphisms (TNF-␣, TNF-␤, IL-1, IL-10, IFN-␥). A study by Stark et al 90 identified an association between chronic GVHD and donor homozygosity for the 196R allele of the TNF type II receptor (TNFRII), associated with decreased TNFRII levels and thus increased functional levels of TNF.…”

Section: Cytokine Therapymentioning

confidence: 99%

“…86 Recipient IL-6 polymorphisms have been associated with chronic GVHD in 2 reports, 89,90 though these studies failed to find an association with other donor or recipient polymorphisms (TNF-␣, TNF-␤, IL-1, IL-10, IFN-␥). A study by Stark et al 90 identified an association between chronic GVHD and donor homozygosity for the 196R allele of the TNF type II receptor (TNFRII), associated with decreased TNFRII levels and thus increased functional levels of TNF. Eternacept, a recombinant soluble TNF inhibitor, has reported activity in 10 steroid-refractory patients with chronic GVHD.…”

Section: Cytokine Therapymentioning

confidence: 99%

New approaches for preventing and treating chronic graft-versus-host disease

Lee

2005

Blood

127

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Despite improvements in the practice of allogeneic hematopoietic stem cell transplantation (HCT) over the last 25 years, chronic graft-versus-host disease (GVHD) remains a substantial problem with little change in the incidence, morbidity, and mortality of this complication. In fact, with increased use of peripheral blood, transplantation of older patients, and less immediate transplantation-related mortality, the prevalence of chronic GVHD may increase. One of the difficulties in combating chronic GVHD is a lack of understanding about the pathophysiology of the syndrome. IntroductionChronic graft-versus-host disease (GVHD) is the most serious and common long-term complication of allogeneic hematopoietic stem cell transplantation (HCT), occurring in 20% to 70% of people surviving more than 100 days. 1,2 Approximately half of affected people have 3 or more involved organs, and treatment typically requires immunosuppressive medications for a median of 1 to 3 years. Because of higher treatment-related (nonrelapse) mortality, chronic GVHD remains the major cause of late death despite its association with a lower relapse rate. 3,4 In addition, secondary malignancies are more common in people with chronic GVHD, particularly of commonly involved tissues such as mouth and skin, suggesting that chronic inflammation, prolonged exposure to immunosuppressive medications, or immune dysregulation facilitates the development of new cancers. 5 Finally, the functional consequences of chronic GVHD organ involvement are major determinants of the health and quality of life of survivors. 6,7 Despite the well-recognized adverse effects of chronic GVHD on the long-term success of allogeneic transplantation, its pathophysiology is poorly understood, and management strategies beyond systemic corticosteroids have not been established.While there are some lessons that can be translated from basic and clinical studies of acute GVHD, several lines of evidence suggest that chronic GVHD is not simply a continuation of acute GVHD, and that separate approaches will be required for its prevention and management. First, except for T-cell depletion and use of umbilical cord blood, the major innovations that have improved acute GVHD rates do not seem to have affected chronic GVHD incidence. Second, while there is significant overlap between the organs involved in acute and chronic GVHD, the distribution of affected organs in chronic GVHD is much broader. Fully evolved chronic GVHD is largely an inflammatory and fibrotic process, while acute GVHD is more likely to reflect apoptosis and necrosis. Although traditionally the boundary between acute and chronic GVHD has been set at 100 days after transplantation, more recent definitions hinge on different clinical manifestations rather than time of onset. Third, while acute GVHD is highly associated with subsequent chronic GVHD, approximately 25% to 35% of chronic GVHD is de novo without any preceding acute manifestations, while 20% to 30% of people who had acute GVHD do not go on to develop chronic GVH...

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Advances in the genomics of allogeneic haemopoietic stem cell transplantation

Mullighan

Bardy

2004

Drug Development Research

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Allogeneic haemopoietic stem cell transplantation is curative for many patients with haematologic disorders. Despite advances in supportive care, complications such as graft-versus-host disease (GVHD) and infection remain important causes of morbidity and mortality after transplantation. Human leukocyte antigen (HLA) matching of donors and recipients is important but does not avoid these complications. Recent studies have shown that non-HLA genetic polymorphisms influence the risk of complications after transplant. Polymorphisms in the genes encoding mediators and targets of GVHD, such as cytokines, adhesion molecules, and minor histocompatibility antigens, are associated with GVHD risk and severity. Particularly in HLA-mismatched transplants, matching of donors and recipients for natural killer cell receptors and ligands may influence disease relapse and survival. Polymorphisms in drug-metabolizing enzymes influence toxicities of immunosuppressive drugs used in transplant protocols. Finally, polymorphisms in mediators of host defence such as mannose-binding lectin, myeloperoxidase, and immunoglobulin receptors influence host immune reconstitution and infection risk after transplant. This novel genetic information offers the opportunity to better predict the risk of complications, to offer intensified immunosuppression to those at highest risk of GVHD, and to intervene with novel therapies. Drug Dev.

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Tumour necrosis factor receptor type II 196M/R genotype correlates with circulating soluble receptor levels in normal subjects and with graft-versus-host disease after sibling allogeneic bone marrow transplantation1

Abstract: Because sTNFRIIs can act as TNF antagonists, the association between recipient and donor TNFRII 196R allele status and acute or extensive chronic GVHD incidence, respectively, may reflect reduced circulating sTNFRII.

Cited by 57 publications

References 28 publications

Genetic polymorphisms predicting the outcome of bone marrow transplants

Genetic polymorphisms predicting the outcome of bone marrow transplants

New approaches for preventing and treating chronic graft-versus-host disease

Advances in the genomics of allogeneic haemopoietic stem cell transplantation

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