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Roberta Rizzo, Ilaria Farina, Daria Bortolotti, Elisa Galuppi, Melissa Padovan, Dario Di Luca, Marcello Govoni
A growing body of evidence indicates a possible involvement of HLA (human leukocyte antigen)-G antigens in rheumatoid arthritis (RA), mainly in the HLA-G dimeric isoform, the most active HLA-G form with the strongest immunosuppression, that showed an excellent anti-inflammatory effect in collagen-induced arthritis model mice. However, the relevance of HLA-G dimers in RA response to methotrexate (MTX) treatment is still unknown. We analyzed the HLA-G dimers' amount in plasma samples from early rheumatoid arthritis (ERA) patients before MTX therapy and evaluated the role of these molecules as biomarker of the different response to the treatment...
October 24, 2016: Clinical Rheumatology
Nadia Ben Fredj, Kaouthar Sakly, Daria Bortolotti, Mouna Aissi, Mahbouba Frih-Ayed, Antonella Rotola, Elisabetta Caselli, Franscesca Cura, Nabil Sakly, Mahjoub Aouni, Dario Di Di Luca, Roberta Rizzo
We aimed to investigate two main polymorphisms in the 3' untranslated region (3'UTR) of the HLA-G gene [14 bp insertion/deletion (INS/DEL) and +3142 C>G] and to assess their impact on the soluble HLA-G (sHLA-G) production in patients with multiple sclerosis (MS). This study included 60 patients with relasping-remitting (RR) MS and 112 healthy donors (HD). Mutations were identified by PCR and PCR-RFLP, and serum sHLA-G quantification was performed by ELISA. For the 14 bp INS/DEL polymorphism, variants frequencies were similar in patients and controls, whereas a significant increased frequency of the +3142 G allele was found in MS patients compared to HD (63...
October 19, 2016: Immunology Letters
Saeide-Sadat Shobeiri, Saeid Abediankenari, Bahareh Lashtoo-Aghaee, Zahra Rahmani, Bahareh Esmaeili-Gorji
BACKGROUND: Research says that diabetes may develop in over 10% of non-diabetic pregnant women. Diabetes which generally occurs late in second trimester and third trimester of pregnancy, it is called gestational diabetes. Overweight or suffering from obesity before pregnancy is type 2 diabetes risk factor. In most cases, diabetic symptoms disappear after delivery. HLA-G has an important role both in mother and fetus tolerance during pregnancy, it may also be effective in the protection of pancreatic islet cells...
2016: Caspian Journal of Internal Medicine
Bor-Show Tzang, Szu-Yi Chiang, Hsu-Chin Chan, Chung-Hsien Liu, Tsai-Ching Hsu
Human parvovirus B19 (B19) is harmful during pregnancy since it can be vertically transmitted to the developing fetus. In addition, the anti‑B19 antibodies induced by B19 infection are believed to have a cytopathic role in B19 transmission; however, knowledge regarding the effects of anti‑B19 antibodies during pregnancy is limited. To investigate the possible roles of anti‑B19 antibodies during pregnancy, the present study examined the effects of anti‑B19‑VP1 unique region (VP1u), anti‑B19‑VP2 and anti‑B19‑nonstructural protein 1 (NS1) immunoglobulin G (IgG) antibodies on BeWo trophoblasts...
September 26, 2016: Molecular Medicine Reports
Paulina Własiuk, Maciej Putowski, Krzysztof Giannopoulos
The appropriate function of the immune system depends on the effective regulation of the immune response on multiple levels. The key element of an effective immune response to antigenic stimulation is maintaining a homeostasis between activation and inhibitory function of immunocompetent cells and molecules. In pathological conditions such as chronic infections, autoimmune diseases or cancer there are significant alterations, and prevalence of signals of one type over another. Main markers of these dysfunctions are altered expressions of molecules, such as programmed death-1 (PD-1), Human Leukocyte Antigen G (HLA-G), or changed percentages of T regulatory cells (Treg)...
October 4, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
A V C Coelho, R R Moura, S Crovella, F Celsi
Human leukocyte antigen (HLA)-G is a key tolerogenic molecule mainly expressed in the placenta and is crucial for implantation of the embryo and immunological tolerance of the fetus during pregnancy. However, under pathological conditions, such as cancer or viral infections, HLA-G can be expressed in other tissues. The gene coding for HLA-G (HLA-G, chromosome 6p21.3) presents numerous polymorphisms, some of them influencing its expression. One of the most studied, is the 14 bp ins/del (rs371194629) situated at the 3'-UTR of the gene...
August 26, 2016: Genetics and Molecular Research: GMR
Federico Carlini, Virginia Ferreira, Stéphane Buhler, Audrey Tous, Jean-François Eliaou, Céline René, Jacques Chiaroni, Christophe Picard, Julie Di Cristofaro
The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood donors...
2016: PloS One
Roberta Rizzo, Liliana Gabrielli, Daria Bortolotti, Valentina Gentili, Giulia Piccirilli, Angela Chiereghin, Claudia Pavia, Silvia Bolzani, Brunella Guerra, Giuliana Simonazzi, Francesca Cervi, Maria Grazia Capretti, Enrico Fainardi, Dario Di Luca, Maria Paola Landini, Tiziana Lazzarotto
Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be expressed as membrane-bound and soluble forms. HLA-G expression increases strongly during viral infections such as congenital human cytomegalovirus (HCMV) infections, with functional consequences in immunoregulation. In this work we investigated the expression of soluble (s)HLA-G and beta-2 microglobulin (component of HLA) molecules in correlation with the risk of transmission and severity of congenital HCMV infection...
2016: Journal of Immunology Research
Nazanin Nazari, Shirin Farjadian
BACKGROUND: HLA-G is a nonclassical HLA class I molecule which, when elevated in tumor cells, is one of the main factors involved in tumor evasion of immune responses including NK and T cells. OBJECTIVE: To evaluate the effect of HLA-G downregulation on NK cell cytotoxicity in tumor cell lines. METHODS: The expression level of HLA-G was measured by real-time PCR and flowcytometry after transfection of SKOV3 by shRNA.1, which targets specific sequences in exon 4, or shRNA...
September 2016: Iranian Journal of Immunology: IJI
Hansjörg Thude, Maike Janssen, Martina Sterneck, Björn Nashan, Martina Koch
Expression of human leukocyte antigen G (HLA-G) has been associated with increased graft survival and decreased rejection episodes. It has been described that the HLA-G 14-base pair (bp) insertion/deletion (ins/del) (rs66554220) and +3142C>G (rs1063320) gene polymorphisms modify the expression level of HLA-G. The aim of the study was to investigate whether these HLA-G polymorphisms have an impact on acute rejection after liver transplantation. In total, 146 liver transplant recipients (57 with acute rejection and 89 without acute rejection) and 99 corresponding liver donors were genotyped for both polymorphisms...
September 21, 2016: Human Immunology
B Issaranggun Na Ayuthaya, P Satravaha, P Pavasant
BACKGROUND AND OBJECTIVE: The cytokine interleukin 12 (IL-12) has been implicated as a potent stimulator of tissue degradation in the pathogenesis of several inflammatory diseases, including periodontitis. In patients with periodontitis, an increased level of IL-12 is found in serum and gingival crevicular fluid. As inflammatory cytokines have been demonstrated to induce activation of the immunomodulatory properties of mesenchymal stem cells (MSCs), this study aimed to investigate the influence of IL-12 on these properties in human periodontal ligament (hPDL) cells...
September 24, 2016: Journal of Periodontal Research
Fabio Morandi, Roberta Rizzo, Enrico Fainardi, Nathalie Rouas-Freiss, Vito Pistoia
HLA-G is a HLA-class Ib molecule with potent immunomodulatory activities, which is expressed in physiological conditions, where modulation of the immune response is required to avoid allograft recognition (i.e., maternal-fetal interface or transplanted patients). However, HLA-G can be expressed de novo at high levels in several pathological conditions, including solid and hematological tumors and during microbial or viral infections, leading to the impairment of the immune response against tumor cells or pathogens, respectively...
2016: Journal of Immunology Research
Priscila Vianna, Andressa Mondadori, Moises E Bauer, Dinara Dornfeld, Jose Artur Chies
During pregnancy the maternal immune system is tolerant to fetal antigens via the engagement of immune regulatory mechanisms. Failure in regulating the maternal immunity to fetal antigens may lead to preeclampsia (PE). We addressed the role of HLAG gene polymorphisms and protein expression as well as regulatory T cells and Th1/Th2/Th17 cytokines in healthy and pathological pregnancies. Blood samples from 26 pregnant women with PE, 25 non-PE and 7 strictly healthy pregnant women were assessed. PBMCs were phenotyped for early activation markers (CD25 and CD69), regulatory T cell markers (CD8+CD28- and CD4+CD25highFoxp3+), ILT-2 (HLA-G receptor) and HLA-G...
September 20, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Cynthia Hernandes Costa, Georgia Fernanda Gelmini, Fabiola Silva Nardi, Valéria Maria Munhoz Sperandio Roxo, Alessandro Schuffner, Maria da Graça Bicalho
HLA-G codes for a non-classical Class I (Ib) protein which is mainly expressed in trophoblast cells. Many pieces of evidence pointed out its essential role conferring immunological tolerance to the fetus. Some HLA-G alleles have been linked to enhanced or reduced HLA-G protein levels expression, which have been associated with reproductive failure. In this study 33 couples undergoing ART (assisted reproduction treatment; n = 66) and 120 couples who conceived naturally (controls; n = 240) were enrolled in the study...
September 8, 2016: Human Immunology
Mohammad Hashemi, Mahnaz Sandoughi, Seyed Amirhossein Fazeli, Gholamreza Bahari, Maryam Rezaei, Zahra Zakeri
Purpose/Background. Mounting evidence designates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. There are controversial reports concerning the impact of HLA-G gene polymorphism on rheumatoid arthritis (RA). This study was aimed at examining the impact of 14 bp ins/del and +3142G>C polymorphism with susceptibility and early disease activity in RA patients in a sample of the Iranian population. Methods. This case-control study was done on 194 patients with RA and 158 healthy subjects...
2016: Advances in Medicine
Fabio Morandi, Sarah Pozzi, Barbara Carlini, Loredana Amoroso, Vito Pistoia, Maria Valeria Corrias
The role of nonclassical HLA-class Ib molecules HLA-G and HLA-E in the progression of Neuroblastoma (NB), the most common pediatric extracranial solid tumor, has been characterized in the last years. Since BM infiltration by NB cells is an adverse prognostic factor, we have here analyzed for the first time the concentration of soluble (s)HLA-G and HLA-E in bone marrow (BM) plasma samples from NB patients at diagnosis and healthy donors. sHLA-G and sHLA-E are present in BM plasma samples, and their levels were similar between NB patients and controls, thus suggesting that these molecules are physiologically released by resident or stromal BM cell populations...
2016: Journal of Immunology Research
L L Nilsson, S Djurisic, A-M N Andersen, M Melbye, D Bjerre, L Ferrero-Miliani, R Hackmon, D E Geraghty, T V F Hviid
The etiological pathways and pathogenesis of preeclampsia have rendered difficult to disentangle. Accumulating evidence points toward a maladapted maternal immune system, which may involve aberrant placental expression of immunomodulatory human leukocyte antigen (HLA) class Ib molecules during pregnancy. Several studies have shown aberrant or reduced expression of HLA-G in the placenta and in maternal blood in cases of preeclampsia compared with controls. Unlike classical HLA class Ia loci, the nonclassical HLA-G has limited polymorphic variants...
October 2016: HLA
Barbara Seliger, Simon Jasinski-Bergner, Dagmar Quandt, Christine Stoehr, Juergen Bukur, Sven Wach, Wolfgang Legal, Helge Taubert, Bernd Wullich, Arndt Hartmann
The non-classical human leukocyte antigen E (HLA-E) expression is frequently overexpressed in tumor diseases, transplants and virus-infected cells and represents an immunomodulatory molecule by binding to the receptors CD94/NKG2A, -B and -C on NK and T cells. Due to its immune suppressive features HLA-E expression might represent an important mechanism of tumors to escape immune surveillance. While an aberrant expression of the non-classical HLA-G antigen in human renal cell carcinoma (RCC) has been demonstrated to be associated with a worse outcome of patients and reduced sensitivity to immune effector cell-mediated cytotoxicity, the expression and function of HLA-E has not yet been analyzed in this tumor entity...
August 31, 2016: Oncotarget
Asako Mori, Hirotaka Nishi, Toru Sasaki, Yuzo Nagamitsu, Rie Kawaguchi, Aikou Okamoto, Masahiko Kuroda, Keiichi Isaka
INTRODUCTION: Hypoxia occurs in the first trimester of placental development and is implicated in the regulation of trophoblast differentiation. Prolonged hypoxic conditions in the placenta are related to the development of preeclampsia. MicroRNAs (miRNAs) are noncoding, single-stranded RNAs that modulate gene expression by targeting messenger RNA. We hypothesized that, under hypoxic conditions, trophoblasts may have a unique miRNA profile that may play a critical role in placental development...
September 2016: Placenta
Layale Yaghi, Isabelle Poras, Renata T Simoes, Eduardo A Donadi, Jörg Tost, Antoine Daunay, Bibiana Sgorla de Almeida, Edgardo D Carosella, Philippe Moreau
HLA-G is an immune checkpoint molecule with specific relevance in cancer immunotherapy. It was first identified in cytotrophoblasts, protecting the fetus from maternal rejection. HLA-G tissue expression is very restricted but induced in numerous malignant tumors such as glioblastoma, contributing to their immune escape. Hypoxia occurs during placenta and tumor development and was shown to activate HLA-G. We aimed to elucidate the mechanisms of HLA-G activation under conditions combining hypoxia-mimicking treatment and 5-aza-2'deoxycytidine, a DNA demethylating agent used in anti-cancer therapy which also induces HLA-G...
August 26, 2016: Oncotarget
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