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The HLA-G genotype is associated with IL-10 levels in activated PBMCs

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Abstract

Human leukocyte antigen (HLA)-G is an MHC class Ib molecule that is expressed at the feto-maternal interface during pregnancy. However, recent results have also shown that it may have important functions as an immuno-modulatory factor in adult life. Differences in the pattern of alternative splicing and in the stability of HLA-G mRNA transcripts have been associated with HLA-G polymorphisms, especially a 14 bp deletion/insertion polymorphism in the 3′ untranslated region of the HLA-G gene. We have investigated the secretion of HLA-G5/soluble HLA-G1 and interleukin-10 (IL-10) in lipopolysaccharide (LPS)-activated peripheral blood mononuclear lymphocytes (PBMCs) in relation to the HLA-G 14 bp genotype. No HLA-G5/sHLA-G1 could be detected in the non-activated control PBMC culture media, and there were no significant differences among the three HLA-G 14 bp genotypes regarding IL-10 concentrations. In LPS-activated PBMC cultures, no significant differences among the three HLA-G 14 bp genotypes regarding HLA-G5/sHLA-G1 concentrations were observed. However, this was in contrast to the IL-10 levels (P=0.0004, Kruskal–Wallis test). The +14/+14 bp PBMC samples expressed higher levels of IL-10 when compared to the −14/+14 bp genotype and the −14/−14 bp genotype. Interestingly, the IL-10 G/G polymorphism at position −1082 was more frequent in the +14/+14 bp genotype (P=0.024, χ2 test). These results support an autocrine loop between HLA-G5/sHLA-G1 and IL-10 expression in activated PBMCs, which may result in higher IL-10 levels in +14/+14 bp HLA-G genotypes.

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  1. Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Via Luigi Borsari 46, 44100, Ferrara, Italy

    Roberta Rizzo, Marina Stignani, Alessandra Balboni, Maria Teresa Grappa, Loredana Melchiorri & Olavio R. Baricordi

  2. Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen, Denmark

    Thomas Vauvert F. Hviid

  3. Department of Experimental and Diagnostic Medicine, Biotechnology Center, University of Ferrara, Via Luigi Borsari 46, 44100, Ferrara, Italy

    Olavio R. Baricordi

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  1. Roberta Rizzo
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Rizzo, R., Hviid, T.V.F., Stignani, M. et al. The HLA-G genotype is associated with IL-10 levels in activated PBMCs. Immunogenetics 57, 172–181 (2005). https://doi.org/10.1007/s00251-005-0788-0

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