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

Lochmanová, Gabriela; Jedlickova, L.; Potěšil, David; Tomancová, Alexandra; Verner, Jan; Pospı́šilová, Šárka; Doubek, Michael; Mayer, Jiřı́; Zdráhal, Zbyněk

doi:10.1002/prca.201100104

Cited by 4 publications

(4 citation statements)

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“…A prospective study using these markers is needed to investigate the early detection rate of liver and colon aGvHD. Early aGvHD detection allows prompt clinical intervention, which in turn may result in an improved HSCT outcome [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Colon and liver tissue damage detection using methylated SESN3 and PTK2B genes in circulating cell-free DNA in patients with acute graft-versus-host disease

Waterhouse

Pennisi

Pfeifer

et al. 2020

Bone Marrow Transplant

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Cell-free DNA (cfDNA) has been investigated in acute graft-versus-host disease (aGvHD) following allogeneic cell transplantation (HSCT). Identifying the tissue of origin of cfDNA in patients with aGvHD is relevant particularly when a biopsy is not feasible. We investigate the cfDNA tissue of origin in patients with aGvHD using methylated gene biomarkers. Patients with liver, colon, or skin aGvHD ( n = 28) were analyzed. Liver- and colon-derived cfDNA was measured using a colon- (SESN3) and liver (PTK2B)-specific methylation marker with digital droplet PCR. A statistically significant difference ( p < 0.001) in PTK2B and SESN3 concentration was observed between patients with colon or liver GvHD and the control group. For SESN3 and PTK2B the area under the curve in the receiver-operating characteristic (ROC) space was 0.952 (95% CI, 0.888–1 p < 0.001) and 0.971 (95% CI, 0.964–1 p < 0.001), respectively. Thresholds to differentiate aGvHD from non-aGvHD in colon were 0 (sensitivity: 0.905; specificity: 0.989) and liver 1.5 (sensitivity: 0.928; specificity: 0.910). Clinical improvement of liver or colon aGvHD resulted in PTK2B and SESN3 reduced concentration. Whereas, in those patients without improvement the PTK2B and SESN3 level remained stable or increased. The PTK2B liver-specific marker and the SESN3 colon-specific marker and their longitudinal analysis might improve aGvHD detection.

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Section: Discussionmentioning

confidence: 99%

Colon and liver tissue damage detection using methylated SESN3 and PTK2B genes in circulating cell-free DNA in patients with acute graft-versus-host disease

Waterhouse

Pennisi

Pfeifer

et al. 2020

Bone Marrow Transplant

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“…Such research was focused on the discovery and validation of GVHD-related essential biomarkers with the main purpose to predict and evaluate the response to therapy, as well as to understand the complex pathophysiology of GVHD. Proteomics is a field with a huge potential impact in the study of GVHD and previously-published papers confirm this hypothesis [ 58 , 67 , 68 ].…”

Section: Protein Dysregulation In Hematological Malignancies and Gvhdmentioning

confidence: 90%

Protein dysregulation in graft versus host disease

et al. 2017

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Allogeneic hematopoietic stem cell transplantation is a well-established treatment for many malignant and non-malignant hematological disorders. As a frequent complication in up to 50% of all patients, graft-versus-host disease is still the main cause for morbidity and non-relapse mortality. Diagnosis is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally-recognized consensus has yet been established. Protein-based biomarkers represent an interesting tool since they have been recently reported to be an important regulator of various cells, including immune cells such as T cells. Therefore, we assume that protein dysregulation is important in the pathogenesis of acute graft versus host disease and their detection might be an possibility in the early diagnosis and monitoring. In this review, we aim to summarize the previous reports of protein biomarkers, focusing on the pathogenesis of the disease and possible implications in diagnostic approaches.

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“…HSCT is currently the only method that can be promoted to cure thalassemia. Despite significant advances in prophylaxis and therapy, acute graft vs. host disease (aGVHD) remains one of the most common and life-threatening complications of allogeneic HSCT (5), resulting in considerable morbidity and mortality (6). The cumulative incidence of grade II-IV aGVHD in children who have received allogeneic HSCT ranges from 28 to 56% (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Activated CD4 + T lymphocyte is a potential biomarker for acute graft-vs.-host disease after hematopoietic stem cell transplantation in children with transfusion-dependent β-thalassemia

Huang

Luo

2022

Front. Pediatr.

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BackgroundAcute graft-vs.-host disease (aGVHD) is still one of the most common and life-threatening complications of allogeneic hematopoietic stem cell transplantation (HSCT). Whether or not the level of activated T lymphocytes rises before the onset of aGVHD is unknown. We explored the possibility of T lymphocytes as biomarkers for early prediction of aGVHD in children with transfusion-dependent β-thalassemia (TDTβ).MethodsWe retrospectively analyzed the characteristics of T lymphocyte subsets before and 14 days after HSCT in children with TDTβ who developed aGVHD. Data from 95 children (Age ≤ 14 years) who underwent allogeneic HSCT from January 2020 to December 2021 were collected. Patients were divided into non-aGVHD group (n = 55) and aGVHD group (n = 40), and aGVHD group was divided into two subgroups: grade I aGVHD (n = 16) and grade II-IV aGVHD (n = 24). Receiver operating characteristic curve (ROC) analysis was performed to predict aGVHD.ResultsBefore preconditioning in non-aGVHD and aGVHD groups, there was no significant difference in all lymphocyte subsets and ratio of CD4 + /CD8 + T cells. On day 14 post-transplantation in non-aGVHD and aGVHD groups, the absolute concentrations per μl blood of T cells, CD4 + T cells, CD8 + T cells, activated CD4 + T cell and NK cells, were 69.73 (14.70, 137.77) and 140.36 (65.06, 293.42), 10.00 (2.35, 23.59) and 35.91 (12.41, 68.71), 37.25 (5.82, 84.36) and 89.99 (35.83, 180.81), 0.52 (0.17, 2.20) and 4.08 (0.91, 11.12), 43.86 (15.00, 91.31) and 26.35 (15.19, 49.39), respectively. On day + 14 (14 days post-transplantation), the differences in all cell subsets and the ratio of CD4 + /CD8 + T cells were not statistically significant between grade I aGVHD and grade II-IV aGVHD subgroups. The absolute concentrations of CD8 + T cells in grade I aGVHD were significantly higher than in grade II-IV aGVHD [128.21 (61.11, 258.91) vs. 60.81 (21.59, 176.38), P = 0.057]. AUC of NK cells, CD8 + T cells, T cells, CD4 + T cells, and CD4 + CD25 + T cells were 0.6275, 0.6839, 0.7068, 0.7241, and 0.7589, and cut-off values were 73.75 (97.50, 34.55), 146.90 (37.50, 94.55), 187.30 (45.00, 90.91), 18.95 (70.00, 72.73), and 3.24 (52.50, 87.27), respectively. The AUC of the combined CD4 + CD25 + T cells and CD8 + T cells, CD4 + CD25 + T cells and T cells, CD4 + CD25 + T cells and CD4 + T cells, CD4 + CD25 + T cells and NK cells, respectively, were 0.7500, 0.7598, 0.7750, and 0.8050.ConclusionOur findings demonstrate that level of activated CD4 + T cells on day + 14 (post-HSCT) is a valuable biomarker for predicting aGVHD in children with TDTβ and CD8 + T cells could likely be a biomarker for severe aGVHD.

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

Cited by 4 publications

References 82 publications

Colon and liver tissue damage detection using methylated SESN3 and PTK2B genes in circulating cell-free DNA in patients with acute graft-versus-host disease

Colon and liver tissue damage detection using methylated SESN3 and PTK2B genes in circulating cell-free DNA in patients with acute graft-versus-host disease

Protein dysregulation in graft versus host disease

Activated CD4 + T lymphocyte is a potential biomarker for acute graft-vs.-host disease after hematopoietic stem cell transplantation in children with transfusion-dependent β-thalassemia

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