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Ana Márquez, Tamara Fernández-Aranguren, Torsten Witte, Miguel A González-Gay, Javier Martín
September 2016: Clinical and Experimental Rheumatology
M R López-Álvarez, W Jiang, D C Jones, J Jayaraman, C Johnson, W O Cookson, M F Moffatt, J Trowsdale, J A Traherne
Leukocyte immunoglobulin-like receptors (LILR) are expressed mostly on myelomonocytic cells where they are mediators of immunological tolerance. Two LILR genes, LILRA3 and LILRA6, exhibit marked copy number variation. We assessed the contribution of these genes to atopic dermatitis (AD) by analysing transmission in 378 AD families. The data indicated that copies of LILRA6 were over-transmitted to affected patients. They are consistent with a contribution of LILR genes to AD. They could affect the equilibrium between activating and inhibitory signals in the immune response...
October 2016: Immunogenetics
Hui Zhi Low, Gerrit Ahrenstorf, Claudia Pommerenke, Nadine Habermann, Klaus Schughart, David Ordóñez, Renata Stripecke, Esther Wilk, Torsten Witte
BACKGROUND: LILRA3 is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells. LILRA3 has a deletion genotype which is associated with multiple immune disorders. In this study, we wanted to analyze the regulation of LILRA3 and its significance in the context of HIV infection. RESULTS: We analyzed a panel of TLR agonists and found that ssRNA40, a TLR8 agonist, is a potent inducer of LILRA3 in healthy individuals. However, this regulation is much diminished in HIV...
2016: Retrovirology
Hongyan An, Chai Lim, Gilles J Guillemin, Ute Vollmer-Conna, William Rawlinson, Katherine Bryant, Nicodemus Tedla
Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS) in different European populations...
2016: PloS One
Hongyan An, Merryn Brettle, Terry Lee, Benjamin Heng, Chai K Lim, Gilles J Guillemin, Megan S Lord, Enrico Klotzsch, Carolyn L Geczy, Katherine Bryant, Thomas Fath, Nicodemus Tedla
Inhibitory proteins, particularly Nogo 66, a highly conserved 66-amino-acid loop of Nogo A (an isoform of RTN4), play key roles in limiting the intrinsic capacity of the central nervous system (CNS) to regenerate after injury. Ligation of surface Nogo receptors (NgRs) and/or leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse orthologue the paired immunoglobulin-like receptor B (PIRB) by Nogo 66 transduces inhibitory signals that potently inhibit neurite outgrowth. Here, we show that soluble leukocyte immunoglobulin-like receptor A3 (LILRA3) is a high-affinity receptor for Nogo 66, suggesting that LILRA3 might be a competitive antagonist to these cell surface inhibitory receptors...
March 15, 2016: Journal of Cell Science
Miguel A Ortiz, Concepción Núñez, David Ordóñez, José C Alvarez-Cermeño, José E Martínez-Rodriguez, Antonio J Sánchez, Rafael Arroyo, Guillermo Izquierdo, Sunny Malhotra, Xavier Montalban, Antonio García-Merino, Elvira Munteis, Antonio Alcina, Manuel Comabella, Fuencisla Matesanz, Luisa M Villar, Elena Urcelay
BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined...
2015: PloS One
Kouyuki Hirayasu, Hisashi Arase
Human leukocyte immunoglobulin-like receptors (LILR) are a family of 11 functional genes encoding five activating (LILRA1, 2, 4-6), five inhibitory (LILRB1-5) and one soluble (LILRA3) form. The number of LILR genes is conserved among individuals, except for LILRA3 and LILRA6, which exhibit copy-number variations. The LILR genes are rapidly evolving and showing large interspecies differences, making it difficult to analyze the functions of LILR using an animal model. LILRs are expressed on various cells such as lymphoid and myeloid cells and the expression patterns are different from gene to gene...
November 2015: Journal of Human Genetics
Paul A Renauer, Guher Saruhan-Direskeneli, Patrick Coit, Adam Adler, Kenan Aksu, Gokhan Keser, Fatma Alibaz-Oner, Sibel Z Aydin, Sevil Kamali, Murat Inanc, Simon Carette, David Cuthbertson, Gary S Hoffman, Servet Akar, Fatos Onen, Nurullah Akkoc, Nader A Khalidi, Curry Koening, Omer Karadag, Sedat Kiraz, Carol A Langford, Kathleen Maksimowicz-McKinnon, Carol A McAlear, Zeynep Ozbalkan, Askin Ates, Yasar Karaaslan, Nursen Duzgun, Paul A Monach, Huseyin T E Ozer, Eren Erken, Mehmet A Ozturk, Ayten Yazici, Ayse Cefle, Ahmet Mesut Onat, Bunyamin Kisacik, Christian Pagnoux, Timucin Kasifoglu, Emire Seyahi, Izzet Fresko, Philip Seo, Antoine G Sreih, Kenneth J Warrington, Steven R Ytterberg, Veli Cobankara, Deborah S Cunninghame-Graham, Timothy J Vyse, Omer N Pamuk, S Ercan Tunc, Ediz Dalkilic, Muge Bicakcigil, Sibel P Yentur, Jonathan D Wren, Peter A Merkel, Haner Direskeneli, Amr H Sawalha
OBJECTIVE: Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. METHODS: Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry...
May 2015: Arthritis & Rheumatology
Yan Du, Yin Su, Jing He, Yue Yang, Yamei Shi, Yong Cui, Cainan Luo, Xinyu Wu, Xu Liu, Fanlei Hu, Xiaoxu Ma, Li Zheng, Jing Zhang, Xianbo Zuo, Yujun Sheng, Lijun Wu, Xuejun Zhang, Jianping Guo, Zhanguo Li
BACKGROUND: Recently, our research group identified the non-deleted (functional) leucocyte immunoglobulin-like receptor A3 (LILRA3) as a new genetic risk for rheumatoid arthritis. OBJECTIVES: To further investigate whether the functional LILRA3 is a new susceptibility factor for other autoimmune diseases-for example, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). METHODS: The LILRA3 deletion polymorphism and its tagging single nucleotide polymorphism rs103294 were genotyped for 1099 patients with SLE, 403 patients with pSS and 2169 healthy controls...
November 2015: Annals of the Rheumatic Diseases
Roshni R Singaraja, Ian Tietjen, G Kees Hovingh, Patrick L Franchini, Chris Radomski, Kenny Wong, Margaret vanHeek, Ioannis M Stylianou, Linus Lin, Liangsu Wang, Lyndon Mitnaul, Brian Hubbard, Michael Winther, Maryanne Mattice, Annick Legendre, Robin Sherrington, John J Kastelein, Karen Akinsanya, Andrew Plump, Michael R Hayden
While genetic determinants strongly influence HDL cholesterol (HDLc) levels, most genetic causes underlying variation in HDLc remain unknown. We aimed to identify novel rare mutations with large effects in candidate genes contributing to extreme HDLc in humans, utilizing family-based Mendelian genetics. We performed next-generation sequencing of 456 candidate HDLc-regulating genes in 200 unrelated probands with extremely low (≤10th percentile) or high (≥90th percentile) HDLc. Probands were excluded if known mutations existed in the established HDLc-regulating genes ABCA1, APOA1, LCAT, cholesteryl ester transfer protein (CETP), endothelial lipase (LIPG), and UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2 (GALNT2)...
August 2014: Journal of Lipid Research
Yan Du, Yong Cui, Xia Liu, Fanlei Hu, Yue Yang, Xinyu Wu, Xu Liu, Xiaoxu Ma, Xianbo Zuo, Yujun Sheng, Xiangyuan Liu, Jianhua Xu, Ping Zhu, Lingyun Sun, Nan Hong, Xuejun Zhang, Jianping Guo, Zhanguo Li
OBJECTIVE: Leukocyte immunoglobulin-like receptor A3 belongs to a family of receptors with inhibitory or activating functions. Since Caucasian individuals lacking LILRA3 have been found to be susceptible to multiple sclerosis and Sjögren's syndrome, we undertook this study to examine whether LILRA3 deletion is a novel genetic risk factor for rheumatoid arthritis (RA) (another autoimmune disease), whether there are sex-specific effects, and whether LILRA3 influences the subtype and severity of RA...
April 2014: Arthritis & Rheumatology
Hui Zhi Low, Sandra Reuter, Michael Topperwien, Nadine Dankenbrink, Dietrich Peest, Gamze Kabalak, Renata Stripecke, Reinhold E Schmidt, Torsten Matthias, Torsten Witte
LILRA3 is the sole soluble member of the LILR family. Previous studies from our group had shown that a 6.7 kb genetic deletion of LILRA3 is associated with MS and Sjögren's syndrome. An impairment of the immune response leads to a predisposition for B-NHL, so we wanted to study whether the deletion of LILRA3 is also a risk factor for B-NHL, as well as the function of LILRA3. We discovered that the frequency of the homozygous LILRA3 deletion was significantly higher in B-NHL (6%) than in blood donors (3%) (P = 0...
2013: PloS One
María R López-Álvarez, Des C Jones, Wei Jiang, James A Traherne, John Trowsdale
Leukocyte immunoglobulin-like receptors (LILR) are cell surface molecules that regulate the activities of myelomonocytic cells through the balance of inhibitory and activation signals. LILR genes are located within the leukocyte receptor complex (LRC) on chromosome 19q13.4 adjacent to KIR genes, which are subject to allelic and copy number variation (CNV). LILRB3 (ILT5) and LILRA6 (ILT8) are highly polymorphic receptors with similar extracellular domains. LILRB3 contains inhibitory ITIM motifs and LILRA6 is coupled to an adaptor with activating ITAM motifs...
February 2014: Immunogenetics
Terry H Y Lee, Ainslie Mitchell, Sydney Liu Lau, Hongyan An, Poornima Rajeaskariah, Valerie Wasinger, Mark Raftery, Katherine Bryant, Nicodemus Tedla
The leukocyte immunoglobulin-like receptor (LILR) A3 is a member of the highly homologous activating and inhibitory receptors expressed on leukocytes. LILRA3 is a soluble receptor of unknown functions but is predicted to act as a broad antagonist to other membrane-bound LILRs. Functions of LILRA3 are unclear primarily because of the lack of high quality functional recombinant protein and insufficient knowledge regarding its ligand(s). Here, we expressed and characterized recombinant LILRA3 (rLILRA3) proteins produced in 293T cells, Escherichia coli, and Pichia pastoris...
November 15, 2013: Journal of Biological Chemistry
Yang Jiao, Li Wang, Xin Gu, Sha Tao, Lu Tian, Rong Na, Zhuo Chen, Jian Kang, Siqun L Zheng, Jianfeng Xu, Jielin Sun, Jun Qi
A recent prostate cancer (PCa) genome-wide association study (GWAS) identified rs103294, a single nucleotide polymorphism (SNP) located on LILRA3, a key component in the regulation of inflammatory inhibition, to be significantly associated with PCa risk in a Chinese population. Because inflammation may be a common etiological risk factor between PCa and benign prostatic hyperplasia (BPH), the current study was conducted to investigate the association of rs103294 with BPH risk. rs103294 was genotyped in a Chinese population of 426 BPH cases and 1,008 controls from Xinhua Hospital in Shanghai, China...
2013: International Journal of Molecular Sciences
Andrzej Wiśniewski, Marta Wagner, Izabela Nowak, Małgorzata Bilińska, Anna Pokryszko-Dragan, Monika Jasek, Piotr Kuśnierczyk
Recently published studies have implicated the deletion polymorphism in LILRA3 gene, as being associated with multiple sclerosis (MS). A total of 309 patients diagnosed with MS and 379 unrelated healthy volunteers were typed for 6.7-kbp deletion in LILRA3 gene. Simultaneously, presence or absence of HLA-DRB1(∗)1501 allele was established to assess the possibility of interaction between LILRA3 deletion and HLA-DRB1(∗)1501 status. In contrast to previous reports, we did not find any association of LILRA3 deletion with MS susceptibility...
March 2013: Human Immunology
Jianfeng Xu, Zengnan Mo, Dingwei Ye, Meilin Wang, Fang Liu, Guangfu Jin, Chuanliang Xu, Xiang Wang, Qiang Shao, Zhiwen Chen, Zhihua Tao, Jun Qi, Fangjian Zhou, Zhong Wang, Yaowen Fu, Dalin He, Qiang Wei, Jianming Guo, Denglong Wu, Xin Gao, Jianlin Yuan, Gongxian Wang, Yong Xu, Guozeng Wang, Haijun Yao, Pei Dong, Yang Jiao, Mo Shen, Jin Yang, Jun Ou-Yang, Haowen Jiang, Yao Zhu, Shancheng Ren, Zhengdong Zhang, Changjun Yin, Xu Gao, Bo Dai, Zhibin Hu, Yajun Yang, Qijun Wu, Hongyan Chen, Peng Peng, Ying Zheng, Xiaodong Zheng, Yongbing Xiang, Jirong Long, Jian Gong, Rong Na, Xiaoling Lin, Hongjie Yu, Zhong Wang, Sha Tao, Junjie Feng, Jishan Sun, Wennuan Liu, Ann Hsing, Jianyu Rao, Qiang Ding, Fredirik Wiklund, Henrik Gronberg, Xiao-Ou Shu, Wei Zheng, Hongbing Shen, Li Jin, Rong Shi, Daru Lu, Xuejun Zhang, Jielin Sun, S Lilly Zheng, Yinghao Sun
Prostate cancer risk-associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk-associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10(-14)) and 19q13...
November 2012: Nature Genetics
Donal J Brennan, Sharon F McGee, Elton Rexhepaj, Darran P O'Connor, Michael Robson, Colm O'Herlihy
BACKGROUND: The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor. METHODS: Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4)...
2011: BMC Pregnancy and Childbirth
Myongchol Ryu, Yong Chen, Jianxun Qi, Jun Liu, Zheng Fan, Gol Nam, Yi Shi, Hao Cheng, George F Gao
Structurally, Group 1 LILR (Leukocyte Immunoglobulin (Ig)-Like Receptor, also known as Ig-like transcripts, ILT; Leukocyte Ig-like receptor, LIR; and CD85) members are very similar in terms of the HLAIs (human leukocyte antigen class I molecules) binding region and were hypothesized that they all bind to HLAIs. As one of the Group 1 LILRs, LILRA3 is the only secretory LILR and may greatly control the inhibitory immune response induced by LILRB1, LILRB2, and other HLA-binding LILR molecules like LILRA1. Nevertheless, little was known about the binding of LILRA3 to HLAIs...
2011: PloS One
Andrew C Edmondson, Peter S Braund, Ioannis M Stylianou, Amit V Khera, Christopher P Nelson, Megan L Wolfe, Stephanie L Derohannessian, Brendan J Keating, Liming Qu, Jing He, Martin D Tobin, Maciej Tomaszewski, Jens Baumert, Norman Klopp, Angela Döring, Barbara Thorand, Mingyao Li, Muredach P Reilly, Wolfgang Koenig, Nilesh J Samani, Daniel J Rader
BACKGROUND: Plasma levels of high-density lipoprotein cholesterol (HDL-C) are known to be heritable, but only a fraction of the heritability is explained. We used a high-density genotyping array containing single-nucleotide polymorphisms (SNPs) from HDL-C candidate genes selected on known biology of HDL-C metabolism, mouse genetic studies, and human genetic association studies. SNP selection was based on tagging SNPs and included low-frequency nonsynonymous SNPs. METHODS AND RESULTS: Association analysis in a cohort containing extremes of HDL-C (case-control, n=1733) provided a discovery phase, with replication in 3 additional populations for a total meta-analysis in 7857 individuals...
April 2011: Circulation. Cardiovascular Genetics
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