Simple Methods for the Detection of HLA-G Variants in Coding and Non-coding Regions

Nückel, Holger; Castelli, Erick C.; Moreau, Philippe; Ochsenfarth, Crista; Horn, Peter A.; Rebmann, Vera

doi:10.1007/978-1-61779-842-9_7

Cited by 3 publications

(3 citation statements)

References 20 publications

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“…PCR products containing the amplified fragment of approximately 350 bp were directly sequenced using the reverse primer employed in the amplification and the Big Dye Terminator kit in an ABI3100 Genetic Analyzer (Applied Biosystems®, Foster City, CA). All polymorphic sites observed at 3’UTR were individually annotated and named according to our previous reports [12,35]. …”

Section: Methodsmentioning

confidence: 99%

Polymorphic Sites at the 3’ Untranslated Region of the HLA-G Gene Are Associated with Differential hla-g Soluble Levels in the Brazilian and French Population

et al. 2013

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HLA-G molecule has well-recognized tolerogenic properties, and the encoding gene shows lower frequency of polymorphism at the coding region but higher variability at regulatory 5’ and 3’ untranslated (3’UTR) regions. At least three 3’UTR polymorphic sites have been associated with HLA-G mRNA regulation, including the 14 base pair (14bp) Insertion/Deletion, +3142C-G and +3187A-G. We studied the association of polymorphic sites at 3’UTR (sequencing analysis, encompassing the 14bp Ins-Del/+3003T-C/+3010C-G/+3027C-A/+3035C-T/+3142C-G/+3187A-G/+3196C-G polymorphic sites) with plasma soluble HLA-G levels (sHLA-G, detected by ELISA) in 187 French and 153 Brazilian healthy individuals. Allele and genotype frequencies were closely similar in both populations; however, Brazilians showed a higher HLA-G 3’UTR haplotype diversity. Considering sHLA-G levels in both populations altogether, individuals presenting 14bp Del/Del showed higher levels compared to 14bpIns/Ins genotype (P <0.05); those presenting +3010C/G showed higher levels compared to the +3010C-C genotype (P< 0.05); those presenting +3027C-C showed higher levels than the +3027A-A genotype (P< 0.05); and those bearing +3035C-C showed higher levels compared to the +3035C-T (P < 0.01) and +3035T-T (P < 0.05) genotypes. The analyses of 3’UTR haplotypes showed that UTR-1 (DelTGCCCGC) was associated with higher expression of sHLA-G, whereas UTR-5 (InsTCCTGAC) and UTR-7 (InsTCATGAC) with lower expression and other UTRs (UTR-2/3/4/6) exhibited intermediate levels. Since the differential expression of HLA-G may be beneficial or harmful depending on the underlying condition, the identification of individuals genetically programmed to differentially express HLA-G may help on defining novel strategies to control the immune response against the underlying disorder.

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Section: Methodsmentioning

confidence: 99%

Polymorphic Sites at the 3’ Untranslated Region of the HLA-G Gene Are Associated with Differential hla-g Soluble Levels in the Brazilian and French Population

et al. 2013

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“…Genotyping of the 14 bp and C/G + 3142 polymorphisms of the HLA-G gene was performed as previously described [24][25][26][27] in 31 out of 32 patients and donors.…”

Section: Genotyping Of 14 Bp and C/g + 3142 Polymorphisms In The 3′utmentioning

confidence: 99%

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

Nardi

Wagner

et al. 2018

Bone Marrow Transplant

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HLA-G is a non-classical class I molecule which induces tolerance in allogeneic situations by inhibition of cytotoxic NK and CD8 + T cells and by induction of regulatory T cells. Concordantly, in solid organ transplantation HLA-G is associated with a lower risk for acute and chronic rejection, whereas its role in allogeneic stem cell transplantation (allo-SCT) is less established. We here present detailed analyses of HLA-G-levels in patients after allo-SCT showing a correlation of elevated soluble HLA-G (sHLA-G) levels with less severe acute (p = 0.06) and chronic GvHD (p = 0.0025) and with a superior overall survival (p = 0.03). Soluble HLA-G levels are also positively correlated with the frequency of regulatory T cells in vivo. These clinical data are corroborated by in vitro analyses showing that patients-derived sHLA-G inhibit allogeneic immune responses. ATG-treatment of patients dominantly affects the sHLA-G levels post allo-SCT. Thus, this study highlights the association of elevated sHLA-G levels with less severe acute and chronic GvHD and provides additional functional analyses elucidating possible tolerance-inducing mechanisms of sHLA-G in the context of allo-SCT.

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“…HLA-G belongs to nonclassical HLA class I family. Although it shares some structural similarities with classical HLA class I, several important differences render HLA-G unique among HLA class I molecules: it displays a low allelic variation, a restricted peptide repertoire [1–3], an unusually high diversity of molecular structures due to alternative splicing of the primary transcript [4–6], and a restricted expression under physiological conditions, which can be upregulated in various situations. HLA-G has originally been discovered on the extravillous cytotrophoblast at the maternal-fetal interface [7].…”

Section: Introductionmentioning

confidence: 99%

HLA-G as a Tolerogenic Molecule in Transplantation and Pregnancy

Rebmann

Nardi

Wagner

et al. 2014

Journal of Immunology Research

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HLA-G is a nonclassical HLA class I molecule. In allogeneic situations such as pregnancy or allograft transplantation, the expression of HLA-G has been related to a better acceptance of the fetus or the allograft. Thus, it seems that HLA-G is crucially involved in mechanisms shaping an allogeneic immune response into tolerance. In this contribution we focus on (i) how HLA-G is involved in transplantation and human reproduction, (ii) how HLA-G is regulated by genetic and microenvironmental factors, and (iii) how HLA-G can offer novel perspectives with respect to therapy.

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Simple Methods for the Detection of HLA-G Variants in Coding and Non-coding Regions

Cited by 3 publications

References 20 publications

Polymorphic Sites at the 3’ Untranslated Region of the HLA-G Gene Are Associated with Differential hla-g Soluble Levels in the Brazilian and French Population

Polymorphic Sites at the 3’ Untranslated Region of the HLA-G Gene Are Associated with Differential hla-g Soluble Levels in the Brazilian and French Population

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

HLA-G as a Tolerogenic Molecule in Transplantation and Pregnancy

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