Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation

Abstract

Organ transplantation is a lifesaving option for patients with advanced diseases. Rejection is regarded as one of the most severe risk factors post-transplantation. A molecule that contributes to immune tolerance and resisting rejection is human leukocyte antigen (HLA)-G, which belongs to the non-classical major histocompatibility complex class (MHC) I family. HLA-G was originally found to play a role during pregnancy to maintain immune tolerance between mother and child. It is expressed in the placenta and detected in several body fluids as soluble factor as well as different membrane isoforms on cells. Recent findings on HLA-G show that it can also play multifaceted roles during transplantation. This review will explain the general characteristics and biological function of HLA-G and summarize the views supporting the tolerogenic and other roles of HLA-G to better understand its role in solid organ transplantation (SOT) and its complications. Finally, we will discuss potential future research on the role of HLA-G in prevention, diagnosis, and treatment in SOT.

An Improved Protocol for Targeted Differentiation of Primed Human Induced Pluripotent Stem Cells into HLA-G-Expressing Trophoblasts to Enable the Modeling of Placenta-Related Disorders

“…Even though HLA-G by itself does not account for all the immunomodulation properties of EVTs, as demonstrated by Tilburgs et al [19], in vitro experiments with HLA-G transfects have demonstrated its immunomodulation effects [32][33][34][35]. This is further supported by the observation that aberrant HLA-G presence after organ transplantation is associated with a greater chance of graft acceptance [36]. This reinforces that EVTs are highly specialized cells.…”

UP‐regulated levels of sHLA‐G in women with a history of RPL in mid‐gestation presumably to achieve ongoing pregnancy

“…Taking in to consideration the literature and our results lot of non‐unanimity is associated with regard to levels of sHLA‐G during various gestational stages and pregnancy complications. In general, increased expression of HLA‐G may reflect an attempt to control the immune derangement 73 . In order to use sHLA‐G as immunological tracer for successful pregnancy longitudinal studies are required tracking sHLA‐G levels from initial to final stages of gestation in association with the outcome of pregnancy (Figure 7).…”

“…In general, increased expression of HLA-G may reflect an attempt to control the immune derangement. 73 In order to use sHLA-G as immunological tracer for successful pregnancy longitudinal studies are required tracking sHLA-G levels from initial to final stages of gestation in association with the outcome of pregnancy (Figure 7).…”

The correlation between soluble human leukocyte antigen (sHLA‐G) levels and +3010 polymorphism

“…Accordingly, numerous studies have been conducted to correlate HLA‐G haplotypes with disease susceptibility/morbidity utilized as a therapy predictor or in transplantation outcome (Amodio & Gregori, 2020). HLA‐G has tolerogenic properties that can help improve the survival rate of the allograft (Liu et al., 2022). Moreover, in 474 pregnancies, HLA‐G protein was found to be associated with a successful pregnancy.…”

“…HLA-G has tolerogenic properties that can help improve the survival rate of the allograft (Liu et al, 2022). Moreover, in 474 pregnancies, HLA-G protein was found to be associated with a successful pregnancy.…”