Serum cytokine levels and acute graft-versus-host disease after HLA-identical hematopoietic stem cell transplantation

Visentainer, Jeane Eliete Laguila; Lieber, Sofia Rocha; Persoli, Ligia B.L.; Vigorito, Afonso Celso; Aranha, Francisco; Eid, Kátia Aparecida de Brito; Oliveira, Gislaine B.; Miranda, Eliana Cristina Martins; de-Souza, Carmino

doi:10.1016/s0301-472x(03)00264-9

Cited by 74 publications

(59 citation statements)

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“…13,14 IL-10 is a well-known suppressive cytokine of T-cell proliferation; previous studies have shown an association between elevated levels of IL-10 and reduced risk of aGVHD. 15,16 The main source of IL-10 is monocytes which in hematopoetic stem cell transplant patients are of donor's origin and hence a donor's low producer genotype would be expected to increase the risk of GVHD.…”

Section: Discussionmentioning

confidence: 99%

Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

et al. 2011

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Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation (allo-HSCT). We retrospectively analyzed specific polymorphisms in genes for interleukin (IL)-10, IL-6, tumor-necrosis factor alpha (TNF-a) and interferon gamma (IFN-c) in a pediatric cohort of 57 histocompatibility leucocyte antigen (HLA)-identical sibling myeloablative transplants. Both recipient and donor genotypes were tested for association with graft-versus-host disease (GVHD) by statistical methods including Cox regression analysis. We found a significant association between the IL-10 promoter haplotype polymorphisms at positions -1082, -819 and -592 with the occurrence of severe (grades III-IV) acute GVHD (aGVHD). Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD (hazard risk (HR)50.20, 95% confidence interval (CI): 0.06-0.67) in comparison with patients with other IL-10 haplotypes (P50.008). Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype (HR50.17, 95% CI: 0.012-0.320) versus other IL-10 haplotypes (P50.03), whereas overall survival was not influenced by IL-10 haplotype polymorphisms. In multivariate analysis, the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development (P50.02, HR50.21, 95% CI: 0.05-0.78). These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.

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Section: Discussionmentioning

confidence: 99%

Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

et al. 2011

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“…15 Acute GVHD has traditionally thought to be a Th1 response, and thus, cytokines including IL-12 and IFN-g have been shown to have correlations with acute GVHD. 12,14,16 IL-18, which induces the production of Th1 cytokines, has been reported by two studies to correlate with acute GVHD, with evidence that IL-18 levels decrease with successful treatment. 17,18 Paradoxically, some studies have shown that cytokines with anti-inflammatory effects are associated with acute GVHD.…”

Section: Il-2mentioning

confidence: 97%

“…As significant inflammation was thought to be a major part of the initial trigger of acute GVHD, early studies focused on acute-phase reactants, such as IL-1 and IL-6, in addition to TNF-a. [11][12][13][14] A Japanese study measured C-reactive protein in a heterogeneous group of over 200 patients with analysis showing that although higher C-reactive protein levels could predict for acute GVHD, other factors including conditioning regimen intensity, infection and unrelated donors were also associated with higher levels. 15 Acute GVHD has traditionally thought to be a Th1 response, and thus, cytokines including IL-12 and IFN-g have been shown to have correlations with acute GVHD.…”

Section: Il-2mentioning

confidence: 99%

“…IL-10, which is thought to downregulate the synthesis of certain cytokines, such as IL-2, TNF-a and IFN-g, has been shown to be elevated in acute GVHD with the theory that it is produced in response to the significant inflammation present. 12,13 Similarly, transforming growth factor b, which has roles in regulatory T-cell development and inhibition of lymphocyte activation, has also been studied. 12 IL-7 and IL-15 are thought to function in the homeostatic peripheral expansion of donor T cells after the lymphodepletion induced by conditioning, and both have been studied.…”

Section: Il-2mentioning

confidence: 99%

“…12,13 Similarly, transforming growth factor b, which has roles in regulatory T-cell development and inhibition of lymphocyte activation, has also been studied. 12 IL-7 and IL-15 are thought to function in the homeostatic peripheral expansion of donor T cells after the lymphodepletion induced by conditioning, and both have been studied. Thiant et al 19 showed that day þ 14 levels of IL-7 could predict for grades II-IV acute GVHD.…”

Section: Il-2mentioning

confidence: 99%

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Biomarkers for acute GVHD: can we predict the unpredictable?

2012

Bone Marrow Transplant

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Acute GVHD remains an important complication after allogeneic hematopoietic cell transplantation (HCT). Many efforts have been devoted to identifying potential noninvasive peripheral blood biomarkers to help improve the diagnosis or management of acute GVHD while avoiding invasive tissue biopsies. Early attempts to identify biomarkers focused on inflammatory cytokines, especially IL-2 or TNF-a, however, both of these and others were not specific for GVHD, often being elevated in the setting of generalized inflammation, accompanying other major complications of HCT as well. More recent efforts have focused on additional cytokines and other cell-surface molecules, which function in leukocyte trafficking and activation with the hope that these can also serve as targets for novel therapeutic approaches. Modern proteomic methods have allowed the screening of large numbers of patient samples and yielded several novel candidate biomarkers, including elafin and reg3a, which may not be directly involved in the immunological pathogenesis of GVHD, but may be unique biomarkers for end-organ injury. Combining these new molecules with traditionally identified cytokines to form an acute GVHD biomarker panel has recently shown the ability to predict outcomes in patients who develop acute GVHD. The ultimate goals of identifying a specific biomarker are to refine diagnosis, guide therapy and develop risk-adapted approaches in order to better treat patients and improve outcomes after allogeneic HCT. These approaches include differential treatment for patients who develop acute GVHD with a high-risk biomarker profile as well as pre-emptive therapy in patients after HCT prior to the development of symptoms. With the recent progress summarized below, these goals may soon be realized.

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Potential biomarkers for early detection of acute graft‐versus‐host disease

Lochmanová

Jedlickova

Potěšil

et al. 2012

Proteomics Clinical Apps

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Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HCT), resulting in considerable morbidity and mortality. Currently, the diagnosis of aGVHD is largely made based on clinical parameters and invasive biopsies. For the past 20 years, researchers have been trying to find reliable biomarkers to enable early and accurate diagnosis of aGVHD. Although a number of potential aGVHD biomarkers have been published, as yet, no validated diagnostic test is available. Proteomics encompasses a broad range of rapidly developing technologies, which have shown tremendous promise for early detection of aGVHD. In this article, we review the current state of aGVHD biomarker discovery, provide a summary of the key proteins of interest and the most common analytical procedures for the clinic, as well as outlining the significant challenges faced in their use.

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Serum cytokine levels and acute graft-versus-host disease after HLA-identical hematopoietic stem cell transplantation

Cited by 74 publications

References 0 publications

Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

Biomarkers for acute GVHD: can we predict the unpredictable?

Potential biomarkers for early detection of acute graft‐versus‐host disease

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