Effect of IL-18 and sIL2R on aGVHD occurrence after hematopoietic stem cell transplantation in some Iranian patients

Shaiegan, Mojgan; Iravani, M.R.; Babaee, Gholam Reza; Ghavamzadeh, Ardeshir

doi:10.1016/j.trim.2005.10.002

Cited by 41 publications

(28 citation statements)

References 18 publications

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“…They observed that IL-18 concentration on day þ 10 correlated with the severity of GVHD, before clinical symptoms developed. 16 More recently other published papers have reported different results on IL-12p70. In a series of reduced intensity conditioning, Mohty's study reported that, among a panel of 10 cytokines, only the IL12p70 level was significantly associated with grade II-IV aGVHD.…”

Section: Discussionmentioning

confidence: 97%

Monitoring of TNFR1, IL-2Rα, HGF, CCL8, IL-8 and IL-12p70 following HSCT and their role as GVHD biomarkers in paediatric patients

Berger¹,

Signorino²,

Muraro³

et al. 2013

Bone Marrow Transplant

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No predictive factors are currently available to establish patient-specific GVHD risk. A panel of six serum cytokines (TNF receptor 1, IL-2 receptor alfa (IL-2Ra), hepatocyte growth factor (HGF), monocyte chemo-attractant protein-2, IL-8, IL-12p70) were monitored at established time points (days À 1, þ 1, þ 7, þ 14, þ 21, þ 28 and þ 60) in 170 paediatric hematopoietic SCT (HSCT) recipients. We found that higher concentrations of IL-2Ra on days þ 14 and þ 21 together with HGF on days þ 14 and þ 21 were significantly associated at a higher probability of both grade II-IV GVHD (on day þ 14 it was: 60% vs 28%, P ¼ 0.007) and grade III-IV (on day þ 14 it was: 40% vs 15%, P ¼ 0.001). The higher IL-8 serum concentration on day þ 28 was associated with a lower probability of chronic GVHD being 4% vs 29% (P ¼ 0.01) for patients with higher vs lower IL-8 serum concentration. These findings were confirmed when the analysis was restricted to the the matched unrelated donor group. In conclusion, even if the serum cytokine levels were related to several variables associated with HSCT, we identified two cytokines as predictors of GVHD II-IV and III-IV, translating into a higher TRM risk (17% vs 3%, P ¼ 0.004).

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Section: Discussionmentioning

confidence: 97%

Monitoring of TNFR1, IL-2Rα, HGF, CCL8, IL-8 and IL-12p70 following HSCT and their role as GVHD biomarkers in paediatric patients

Berger¹,

Signorino²,

Muraro³

et al. 2013

Bone Marrow Transplant

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“…[53][54][55][56][57] In 2 studies, IL-18 concentrations were closely correlated with IL-2R␣ concentrations, and IL-2R␣ concentrations with GVHD severity. 56 However, some studies found that sIL-2R␣ concentrations were also increased in patients with other transplantation-related complications, such as veno-occlusive disease and sepsis. 53 Similarly, TNF-␣ and its receptors, particularly TNFR1 concentrations, were higher in aGVHD patients than in patients without GVHD.…”

Section: Biomarkers Identified Using the Pathology Of Agvhd Systemic mentioning

confidence: 99%

Discovery and validation of graft-versus-host disease biomarkers

Paczesny

2013

Blood

132

114

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective tumor immunotherapy available. Although allo-HSCT provides beneficial graft-versus-tumor effects, acute GVHD (aGVHD) is the primary source of morbidity and mortality after HSCT. Diagnosis of aGVHD is typically based on clinical symptoms in one or more of the main target organs (skin, liver, gastrointestinal tract) and confirmed by biopsy. However, currently available diagnostic and staging tools often fail to identify patients at higher risk of GVHD progression, unresponsiveness to therapy, or death. In addition, there are shortcomings in the prediction of GVHD before clinical signs develop, indicating the urgent need for noninvasive and reliable laboratory tests. Through the continuing evolution of proteomics technologies seen in recent years, plasma biomarkers have been identified and validated as promising diagnostic tools for GVHD and prognostic tools for nonrelapse mortality. These biomarkers may facilitate timely and selective therapeutic intervention but should be more widely validated and incorporated into a new grading system for risk stratification of patients and better-customized treatment. This review identifies biomarkers for detecting GVHD, summarizes current information on aGVHD biomarkers, proposes future prospects for the blinded evaluation of these biomarkers, and discusses the need for biomarkers of chronic GVHD. (Blood. 2013;121(4):585-594) IntroductionAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a widely used therapy for a variety of malignant and nonmalignant hematologic diseases. In malignant disease, the donor immune system recognizes residual tumor cells as foreign and eradicates them by immunologic means, known as the graft-versustumor (GVT) effect. Unfortunately, donor immune cells may also attack normal host tissue, particularly the skin, liver, and gastrointestinal (GI) tract, resulting in acute GVHD (aGVHD). GVHD remains one of the major barriers to a more widespread and successful application of allo-HSCT. Known risk factors that increase the incidence and severity of aGVHD include the use of HLA-mismatched unrelated donors rather than HLA-matched sibling donors. 1 A major barrier to GVHD research and treatment is that diagnosis and prognosis rely almost entirely on the presence of clinical symptoms and should be confirmed by biopsy of the involved target organs. No currently used laboratory tests can predict the risk of developing GVHD, responsiveness to treatment, or patient survival. The importance of biomarkers in HSCT settings is crucial because the ability to identify patients at high risk for GVHD early in their transplantation and treatment course has important therapeutic consequences, including more stringent monitoring and/or preventive care. The ability to identify patients who will not respond to traditional treatment and are at particularly high risk for subsequent morbidity and mortality could enable tailored treatment plans, such as additional immunosuppressive...

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“…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. 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.…”

Section: Il-2mentioning

confidence: 99%

“…Recently, investigators from the University of Michigan spearheaded an effort to evaluate the prognostic value of a panel of biomarkers comprised of TNFR1, IL-2Ra, IL-8, HGF, elafin and reg3a. Samples T-cell growth factor, stimulates production of TNF-a and IFN-g Activated NK cells, induces IFN-g production Nakamura et al 16 Fujimori et al 17 Shaiegan et al 18 Mohty et al Visentainer et al 12 Visentainer et al 12 Liem et al 13 Other circulating molecules Uguccioni et al 20 Okamoto et al 21 Luft et al 22 Seidel et al 23 Kircher et al 24 Hubel et al 26 Chen et al 25 Lymphocytetrafficking molecules a4b7 integrin…”

Section: Moving Toward Risk-adapted Approachesmentioning

confidence: 99%

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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Effect of IL-18 and sIL2R on aGVHD occurrence after hematopoietic stem cell transplantation in some Iranian patients

Cited by 41 publications

References 18 publications

Monitoring of TNFR1, IL-2Rα, HGF, CCL8, IL-8 and IL-12p70 following HSCT and their role as GVHD biomarkers in paediatric patients

Monitoring of TNFR1, IL-2Rα, HGF, CCL8, IL-8 and IL-12p70 following HSCT and their role as GVHD biomarkers in paediatric patients

Discovery and validation of graft-versus-host disease biomarkers

Biomarkers for acute GVHD: can we predict the unpredictable?

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