Level of Granzyme B-positive T-regulatory cells is a strong predictor biomarker of acute Graft-versus-host disease after day +30 after allo-HSCT

Drokov, Mikhail; Davydova, Julia; Кузьмина, Л А; Galtseva, Irina; Kapranov, Nikolay; Vasilyeva, Vera; Dubnyak, D S; Koroleva, O M; Mikhalcova, Ekaterina D.; Popova, Natalia N.; Паровичникова, Е Н; Vg, Savchenko

doi:10.1016/j.leukres.2017.01.014

Cited by 9 publications

(7 citation statements)

References 32 publications

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“…To our knowledge, this subset has not been linked to cGVHD before. However, one recent study did identify another GzB positive subset linked to acute GVHD development (29). They assessed levels of GzB positive regulatory T-cells 30 days post-HSCT and found these to be present at elevated levels in patients with acute GVHD.…”

Section: Discussionmentioning

confidence: 99%

“…Validating the results in independent cohorts, preferably at a different center, is crucial before a marker may be considered to be used as a biomarker (32). In addition, in future studies performing a receiver operating characteristic (ROC) analysis to assess the prognostic potential of the markers would be vital, as has been done in many biomarker studies, both for acute and cGVHD (10, 11, 13, 14, 16, 25, 28, 29, 57). Unfortunately, the sample size in this study was insufficient to perform an ROC analysis correctly.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, several studies have focused on identifying cellular subsets to utilize as potential biomarkers, be it for acute (28, 29) or cGVHD (20, 24, 30, 31). …”

Section: Introductionmentioning

confidence: 99%

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Combining Flow and Mass Cytometry in the Search for Biomarkers in Chronic Graft-versus-Host Disease

et al. 2017

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Chronic graft-versus-host disease (cGVHD) is a debilitating complication arising in around half of all patients treated with an allogeneic hematopoietic stem cell transplantation. Even though treatment of severe cGVHD has improved during recent years, it remains one of the main causes of morbidity and mortality in affected patients. Biomarkers in blood that could aid in the diagnosis and classification of cGVHD severity are needed for the development of novel treatment strategies that can alleviate symptoms and reduce the need for painful and sometimes complicated tissue biopsies. Methods that comprehensively profile complex biological systems such as the immune system can reveal unanticipated markers when used with the appropriate methods of data analysis. Here, we used mass cytometry, flow cytometry, enzyme-linked immunosorbent assay, and multiplex assays to systematically profile immune cell populations in 68 patients with varying grades of cGVHD. We identified multiple subpopulations across T, B, and NK-cell lineages that distinguished patients with cGVHD from those without cGVHD and which were associated in varying ways with severity of cGVHD. Specifically, initial flow cytometry demonstrated that patients with more severe cGVHD had lower mucosal-associated T cell frequencies, with a concomitant higher level of CD38 expression on T cells. Mass cytometry could identify unique subpopulations specific for cGVHD severity albeit with some seemingly conflicting results. For instance, patients with severe cGVHD had an increased frequency of activated B cells compared to patients with moderate cGVHD while activated B cells were found at a reduced frequency in patients with mild cGVHD compared to patients without cGVHD. Moreover, results indicate it may be possible to validate mass cytometry results with clinically viable, smaller flow cytometry panels. Finally, no differences in levels of blood soluble markers could be identified, with the exception for the semi-soluble combined marker B-cell activating factor/B cell ratio, which was increased in patients with mild cGVHD compared to patients without cGVHD. These findings suggest that interdependencies between such perturbed subpopulations of cells play a role in cGVHD pathogenesis and can serve as future diagnostic and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Combining Flow and Mass Cytometry in the Search for Biomarkers in Chronic Graft-versus-Host Disease

et al. 2017

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“…Extensive research has been dedicated to identifying blood biomarkers for aGvHD to improve diagnosis and facilitate personalized treatment. Biomarkers for aGvHD have been studied thoroughly at the facets of cytokines (15)(16)(17), immune cells (18)(19)(20)(21), single nucleotide polymorphisms (22), miRNAs (23)(24)(25)(26)(27), and insight.jci.org https://doi.org/10.1172/jci.insight.129494…”

Section: Introductionmentioning

confidence: 99%

A distinct glycerophospholipid metabolism signature of acute graft versus host disease with predictive value

Liu¹,

Huang

Chen

et al. 2019

JCI Insight

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BACKGROUND. Acute graft versus host disease (aGvHD) is a major factor that limits the successful outcomes of allogeneic hematopoietic cell transplantation (alloHSCT). Currently, there are few validated biomarkers that can help predict the risk of aGvHD in clinical settings. METHODS.We performed an integrated metabolomics and transcriptomics study and identified biomarkers that distinguish alloHSCT recipients with aGvHD from alloHSCT recipients without aGvHD in 2 separate cohorts. RESULTS.Pathway analysis of 38 significantly altered metabolites and 1,148 differentially expressed genes uncovered a distinctly altered glycerophospholipid (GPL) metabolism network. Subsequently, we developed an aGvHD risk score (GRS) based on 5 metabolite markers from GPL metabolism to predict the risk of aGvHD. GRS showed a positive predictive value of 92.2% and 89.6% in the training and validation cohorts, respectively. In addition, high GRS was correlated with poor overall survival. Gene expressions of GPL-related lipases were significantly altered in aGvHD samples, leading to dysregulated GPLs. CONCLUSION.Using integrative "Omic" analysis, we unraveled a comprehensive view of the molecular perturbations underlying the pathogenesis of aGvHD. Our work represents an initial investigation of a unique metabolic and transcriptomic network that may help identify aGvHD at an early stage and facilitate preemptive therapy.

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“…С «неполной» реконституцией, то есть в первую очередь неполным восстановлением количества иммунокомпетентных клеток, связано развитие различных осложнений, и в первую очередь тяжелых инфекционных осложнений как в раннем посттрансплантационном периоде (до +100 дня после алло-ТГСК), так и в более позднем [2]. Кроме этого, функциональные особенности и взаимодействие различных иммунокомпетентных клеток обусловливают развитие иммунологических реакций -«трансплантат против опухоли» (РТПО) и «трансплантат против хозяина» (РТПХ) [3,4].…”

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Reconstitution of T-cell-mediated immunity in patients after allogeneic stem cell transplantation

Popova¹,

Савченко²

2020

Gematologiâ i transfuziologiâ

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Background. The timely reconstitution of the donor-derived immune system is a key factor in the prevention of such post-transplant complications as graft versus host disease, relapse or secondary tumours and various infections. These complications affect the long-term survival of patients after allogeneic stem cell transplantation.Aim — to describe the main stages of T Cell–mediated immune recovery in patients after allogeneic stem cell transplantation.General ﬁndings. T-cell–mediated immunity is responsible for anti-infective and anti-tumour immune response. The early post-transplant period is characterized by the thymus-independent pathway of T-cell recovery largely involving proliferation of mature donor T cells, which were transplanted to the patient together with hematopoietic stem cells. To a lesser extent, this recovery pathway is realized through the expansion of host naïve and memory T cells, which survived after conditioning. Thymus-dependent reconstitution involves generation of de novo naïve T cells and subsequent formation of a pool of memory T-cells providing the main immunological effects — graft versus tumour and graft versus host reactions. A better understanding of the T-cell immune reconstitution process is important for selecting optimized pre-transplant conditioning regimens and patient-speciﬁc immunosuppressive therapy approaches, thus reducing the risks of post-transplant complications and improving the long-term survival of patients after allogeneic stem cell transplantation.

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Level of Granzyme B-positive T-regulatory cells is a strong predictor biomarker of acute Graft-versus-host disease after day +30 after allo-HSCT

Cited by 9 publications

References 32 publications

Combining Flow and Mass Cytometry in the Search for Biomarkers in Chronic Graft-versus-Host Disease

Combining Flow and Mass Cytometry in the Search for Biomarkers in Chronic Graft-versus-Host Disease

A distinct glycerophospholipid metabolism signature of acute graft versus host disease with predictive value

Reconstitution of T-cell-mediated immunity in patients after allogeneic stem cell transplantation

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