Soluble Human Leukocyte Antigen G Molecule Expression in Allogeneic Hematopoietic Stem Cell Transplantation: Good Predictor of Acute Graft-versus-Host Disease

Abstract

Background: Graft-versus-host disease (GVHD) remains a main complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Human leukocyte antigen G (HLA-G) is a non-classical class I molecule exerting multiple immunoregulatory functions. The aim of this study was to explore the relationship between soluble HLA-G (sHLA-G) and GVHD after allo-HSCT. Methods: The sHLA-G levels were examined using enzyme-linked immunosorbent assay in patients with hematological malignancies (n = 106) before transplantation, on days +15 and +30 after transplantation, as well as healthy volunteers (n = 10). Results: The levels of sHLA-G5, sHLA-G6 and sHLA-G7 in patients on days +15 and +30 after transplantation were all significantly higher than those before transplantation (all p ≤ 0.001). The increased levels of sHLA-G5 on days +15 and +30 after transplantation were both significantly higher in patients with grade 0-I acute GVHD (aGVHD) compared to those with grade II-IV aGVHD (both p < 0.001). The increased levels of sHLA-G5 on days +15 and +30 after transplantation were both negatively correlated with the severity of aGVHD (both p < 0.001). Conclusion: sHLA-G5 might be a predictor of the occurrence and severity of aGVHD, which may help to establish individual prophylaxis against aGVHD and improve the survival for patients after allo-HSCT.

The role of soluble HLA-G and HLA-G receptors in patients with hematological malignancies after allogeneic stem cell transplantation

“…Literature data point to the important role of HLA-G molecule in the occurrence of GVHD and to the correlation between HLA-G level in patients' blood serum following allotransplantation and the severity of GVHD. Liu et al [20] confirmed that HLA-G5 level may play the role of a prognostic factor for the development of GVHD and the clinical course of this reaction.…”

Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation

“…In the first 30 days after HCT, levels of the soluble G5, G6 and G7 proteins were significantly higher compared to pre-transplant levels; higher levels of soluble HLA-G proteins were found in patients without GVHD compared to lower levels in patients who developed grades II–IV acute GVHD 89 . Very intriguing data on the recovery of CD14 + HLA-G + cells in the plasma of healthy and transplant patients and the ability to antagonize the suppressive function of these cells through HLA-G blockade provide new information on the contribution of HLA-G-expressing monocytes in the immune response 87 .…”

“…Although it has classically been considered that HLA-G expression is restricted to the maternal-fetal interface, the thymus, and the cornea, several recent studies have found increased levels of HLA-G in the plasma 87– 89 and in GVHD target organs in patients receiving allogeneic HCTs 87 . In the first 30 days after HCT, levels of the soluble G5, G6 and G7 proteins were significantly higher compared to pre-transplant levels; higher levels of soluble HLA-G proteins were found in patients without GVHD compared to lower levels in patients who developed grades II–IV acute GVHD 89 .…”

HLA-G as a Tolerogenic Molecule in Transplantation and Pregnancy

“…Indeed, increased HLA-G5 levels on day 15 and on day 30 after HCST seem to be negatively correlated with the severity of aGvHD [109] suggesting HLA-G5 as a predictor of the occurrence and severity of aGvHD. This concept has been further sustained by the fact that high levels of HLA-G before and after allograft are indicative for good HCST outcome with respect to the occurrence of aGvHD.…”