Elevated soluble human leukocyte antigen G levels in patients after allogeneic stem cell transplantation are associated with less severe acute and chronic graft-versus-host disease

Kordelas, Lambros; Nardi, Fabiola da Silva; Wagner, Bettina; Ditschkowski, Markus; Liebregts, Tobias; Lindemann, Monika; Heinemann, Falko M.; Horn, Peter A.; Beelen, Dietrich; Rebmann, Vera

doi:10.1038/s41409-018-0145-1

Cited by 9 publications

(10 citation statements)

References 37 publications

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“…Anti‐thymocyte globulin treatment of patients dominantly affects the sHLA‐G levels post allogeneic stem cell transplant. Thus, this study highlights the association of elevated sHLA‐G levels with less severe acute and chronic GvHD and overall survival (Kordelas et al., 2018).…”

Section: Transplantationsupporting

confidence: 58%

“…The involvement of HLA‐G has also been considered in bone marrow transplantation. Recently, Kordelas and colleagues (Kordelas et al., 2018) measured sHLA‐G levels in patients undergoing allo stem cell transplantation (SCT) and reported a correlation of elevated soluble HLA‐G (sHLA‐G) levels with less severe acute and chronic GvHD and with a superior overall survival. Moreover, sHLA‐G levels are also positively correlated with the frequency of regulatory T cells in vivo.…”

Section: Transplantationmentioning

confidence: 99%

“…14The HLA-G expression status as well as the disease stage can predict relapse in ovarian carcinoma (OR = 4.11, 95% CI: 0.946-17.905; p = .059). 15 Regardless of the effects of these polymorphisms in the success of the allograft, it has been shown that the HLA-G soluble isoforms had protective effect against graft rejection in solid organ transplantation or the graft-versus-host disease (GvHD) in SCT (Kordelas et al, 2018). In vitro analyses have shown that sHLA-G inhibit allogeneic immune responses.…”

Section: Tr An S Pl Antati Onmentioning

confidence: 99%

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HLA‐G: Function, polymorphisms and pathology

Arnaiz‐Villena

Juárez

Suárez-Trujillo

et al. 2020

Int J Immunogenetics

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HLA‐G immune modulatory genes and molecules are presently being studied by a widespread number of research groups. In the present study, we do not aim to be exhaustive since the number of manuscripts published every year is overwhelming. Instead, our aim is pointing out facts about HLA‐G function, polymorphism and pathology that have been confirmed by several different researchers, together with exposing aspects that may have been overlooked or not sufficiently remarked in this productive field of study. On the other hand, we question whether performing mainly studies on HLA‐G and disease associations is going to give a clear answer in the future, since 40 years of study of classical HLA molecules association with disease has still given no definite answer on this issue.

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Section: Transplantationsupporting

confidence: 58%

Section: Transplantationmentioning

confidence: 99%

Section: Tr An S Pl Antati Onmentioning

confidence: 99%

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HLA‐G: Function, polymorphisms and pathology

Arnaiz‐Villena

Juárez

Suárez-Trujillo

et al. 2020

Int J Immunogenetics

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“…In recent years, the non-classical HLA-molecules have gained increasing attention with respect to their role regarding clinical endpoints in HSCT. We have previously investigated the influence of the non-classical HLA-molecule HLA-G after HSCT and observed in 32 patients a correlation of elevated soluble HLA-G levels with less severe acute or chronic GvHD, and with a superior overall survival (23). Here, we present data on the role of the non-classical HLA-molecule HLA-E in a larger cohort of 93 patients.…”

Section: Discussionmentioning

confidence: 90%

“…However, the studies have described partly contradictory results regarding the influence of the three most frequent genotypes (HLA-E * 01:01/01:01, HLA-E * 01:01/01:03, HLA-E * 01:03/01:03) on transplant-related mortality (TRM), acute, and chronic GvHD, relapse, disease free survival (DFS), and overall survival (OS) after HSCT (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). We have previously observed in a cohort of 32 patients that elevated soluble HLA-G levels after HSCT are associated with less severe acute and chronic GvHD (23). Here, we investigated soluble HLA-E (sHLA-E) levels in 93 patients post-HSCT and HLA-E genotypes of donor and recipient pairs.…”

Section: Introductionmentioning

confidence: 99%

Decreased Soluble Human Leukocyte Antigen E Levels in Patients After Allogeneic Hematopoietic Stem Cell Transplantation Are Associated With Severe Acute and Extended Chronic Graft-versus-Host Disease and Inferior Overall Survival

et al. 2020

Self Cite

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HLA-E is a member of the non-classical HLA molecules and by interaction with activating or inhibitory receptors of NK and T cells, HLA-E can lead to immune activation or suppression context-dependently. Recently, the non-classical HLA molecules gain more attention in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). Most studies so far have focused on the two most frequent genotypes (HLA-E * 01:01 and HLA-E * 01:03) and investigated their potential association with clinical endpoints of HSCT, like graft-versus-host disease (GvHD), relapse, and overall survival (OS). However, these studies have produced inconsistent results regarding the role of HLA-E and the clinical endpoints after HSCT. We therefore here investigate the amount of soluble HLA-E (sHLA-E) in patients following HSCT and relate this to the clinical endpoints after HSCT. In univariate analysis, we observe a significant association of reduced levels of sHLA-E with severe acute GvHD, extended chronic GvHD and with inferior OS. Using receiver operating characteristic analyses specific thresholds obtained 1, 2, or 3 month(s) after HSCT were identified being indicative for severe acute GvHD, extended chronic GvHD, or inferior OS. In subgroup analyses, this effect can be confirmed in patients not treated with ATG, but is derogated in ATG-treated patients. Notably, we could not detect any association of the course of sHLA-E levels post-HSCT with the three most frequent HLA-E genotypes (HLA-E * 01:03/ * 01:03, HLA-E * 01:01/ * 01:01, HLA-E * 01:01/ * 01:03). However, with regard to 5-year-OS there was an association of HLA-E * 01:03 homozygosity with inferior OS. Taking ATG-treatment, recipient and donor HLA-E genotypes into consideration among other well-known risk factors, the sHLA-E status was found as an independent predictor for the development of extended cGvHD Kordelas et al. Soluble HLA-E and HSCT and inferior OS following HSCT irrespective of the sHLA-E thresholds. These findings shed some light on the possible impact of reduced sHLA-E levels after HSCT on GvHD and OS. Thus, sHLA-E appears to be a novel promising candidate for the prediction of clinical HSCT outcome with regards to extended cGvHD and OS.

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Functional Role of Circular RNA in Regenerative Medicine

Cao

Dai

et al. 2018

Advances in Experimental Medicine and Biology

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Elevated soluble human leukocyte antigen G levels in patients after allogeneic stem cell transplantation are associated with less severe acute and chronic graft-versus-host disease

Cited by 9 publications

References 37 publications

HLA‐G: Function, polymorphisms and pathology

HLA‐G: Function, polymorphisms and pathology

Decreased Soluble Human Leukocyte Antigen E Levels in Patients After Allogeneic Hematopoietic Stem Cell Transplantation Are Associated With Severe Acute and Extended Chronic Graft-versus-Host Disease and Inferior Overall Survival

Functional Role of Circular RNA in Regenerative Medicine

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