Genetic Polymorphism of HLA-G 14-bp Insertion/Deletion in Pancreas Transplant Recipients and Its Association With Type 1 Diabetes Mellitus

Rezaei, Firoozeh; Zareei, Neda; Razmi, Nematollah; Nikeghbalian, Saman; Azarpira, Negar

doi:10.6002/ect.2018.0162

Cited by 9 publications

(8 citation statements)

References 37 publications

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“…Such type of studies has also been carried out in organ‐specific autoimmune diseases. Thus, in type 1 diabetes, the HLA‐G 14 bp INS genotype was reported to be a diabetes risk factor and might, therefore, be involved in the pathogenesis of the disease (Rezaei et al, 2019).…”

Section: Hla‐g and Diseasementioning

confidence: 99%

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: Hla‐g and Diseasementioning

confidence: 99%

HLA‐G: Function, polymorphisms and pathology

Arnaiz‐Villena

Juárez

Suárez-Trujillo

et al. 2020

Int J Immunogenetics

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“…In the context of the Cusp theory, however, it is important to mention that HLA-G immune modulatory effect has been documented in several autoimmune conditions as well. For example, polymorphisms in the HLA-G gene have been found to be a significant risk factor for type 1 diabetes (128), systemic lupus erythematosus (129,130), RA (131), experimental autoimmune uveitis (132), systemic sclerosis (130), as well as multiple sclerosis and several autoimmune skin conditions (133), asthma (134) and Graves' disease (135), however, it is important to mention that results for associations between HLA-G and diseases are often times contradictory or inconclusive, and warrant further investigation.…”

Section: Immune Modulatory and Autoimmune Disease Effectsmentioning

confidence: 99%

HLA-G and the MHC Cusp Theory

2022

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Human leukocyte antigens (HLA) are significant genetic risk factors in a long list of diseases. However, the mechanisms underlying these associations remain elusive in many cases. The best-characterized function of classical major histocompatibility complex (MHC) antigens is to allow safe presentation of antigenic peptides via a self/non-self-discrimination process. Therefore, most hypotheses to date have posited that the observed associations between certain HLA molecules and human diseases involve antigen presentation (AP). However, these hypotheses often represent inconsistencies with current knowledge. To offer answers to the inconsistencies, a decade ago we have invoked the MHC Cusp theory, postulating that in addition to its main role in AP, the MHC codes for allele-specific molecules that act as ligands in a conformationally-conserved cusp-like fold, which upon interaction with cognate receptors can trigger MHC-associated diseases. In the ensuing years, we have provided empirical evidence that substantiates the theory in several HLA-Class II-associated autoimmune diseases. Notably, in a recent study we have demonstrated that HLA-DRB1 alleles known to protect against several autoimmune diseases encode a protective epitope at the cusp region, which activates anti-inflammatory signaling leading to transcriptional and functional modulatory effects. Relevant to the topic of this session, cusp ligands demonstrate several similarities to the functional effects of HLA-G. The overall goal of this opinion article is to delineate the parallels and distinctive features of the MHC Cusp theory with structural and functional aspects of HLA-G molecules.

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“…As shown in Table 1 , most of the clinical studies showed that tissue or blood expression of HLA-G with any of the above mentioned techniques has a protective role, induction of immune tolerance and subsequent graft acceptance in transplantation. In some studies however, the relation with graft acceptance was not so clear and in these studies expression of HLA-G was determined by time after transplantation ( 96 ), inflammatory processes, or specific genotypes associated with diabetes ( 110 , 123 ) (see Table 1 ). The study by Moroso et al.…”

Section: Transplantationmentioning

confidence: 99%

“…In studies concerning the HLA-G polymorphisms, it has been shown that HLA-G polymorphism can act as a risk factor for diabetes mellitus in both kidney and pancreas transplantation ( 106 , 123 ). Both HLA-G 14bp and +3142G/G show associations with obesity post kidney transplantation ( 92 , 106 ).…”

Section: Transplantationmentioning

confidence: 99%

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

et al. 2022

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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.

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Genetic Polymorphism of HLA-G 14-bp Insertion/Deletion in Pancreas Transplant Recipients and Its Association With Type 1 Diabetes Mellitus

Cited by 9 publications

References 37 publications

HLA‐G: Function, polymorphisms and pathology

HLA‐G: Function, polymorphisms and pathology

HLA-G and the MHC Cusp Theory

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

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