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https://www.readbyqxmd.com/read/28629435/eculizumab-treatment-stochastic-occurrence-of-c3-binding-to-individual-pnh-erythrocytes
#1
Michela Sica, Tommaso Rondelli, Patrizia Ricci, Maria De Angioletti, Antonio M Risitano, Rosario Notaro
BACKGROUND: C5 blockade by eculizumab prevents complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). However, C3-bound PNH red blood cells (RBCs), arising in almost all treated patients, may undergo extravascular hemolysis reducing clinical benefits. Despite the uniform deficiency of CD55 and of CD59, there are always two distinct populations of PNH RBCs, with (C3+) and without (C3-) C3 binding. METHODS: To investigate this paradox, the phenomenon has been modeled in vitro by incubating RBCs from eculizumab untreated PNH patients with compatible sera containing eculizumab, and by assessing the C3 binding after activation of complement alternative pathway...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28614920/-role-of-complement-regulatory-protein-cd55-in-the-liver-immune-injury-of-trichloroethylene-sensitized-mice
#2
X Wang, C Zhang, X D Yang, B D Li, D D Zang, P Yang, J X Zhang, Q X Zhu
Objective: To explore the expression of CD55 in liver tissue of trichloroethylene-sensitized mice and discuss the role of CD55 in the liver immune injury of trichloroethylene-sensitized mice. Methods: 6-8 weeks specific pathogen free female BALB/c were randomly divided into blank control group, solvent control group and TCE treatment group to establish BALB/c mice sensitized model. According to mouse skin sensitization reaction score, TCE treatment mice were divided into sensitized and non-sensitized group at 24 h after the last challenge...
April 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28594911/candidate-genes-on-murine-chromosome-8-are-associated-with-susceptibility-to-staphylococcus-aureus-infection-in-mice-and-are-involved-with-staphylococcus-aureus-septicemia-in-humans
#3
Qin Yan, Sun Hee Ahn, Felix Mba Medie, Batu K Sharma-Kuinkel, Lawrence P Park, William K Scott, Hitesh Deshmukh, Ephraim L Tsalik, Derek D Cyr, Christopher W Woods, Chen-Hsin Albert Yu, Carlton Adams, Robert Qi, Brenda Hansen, Vance G Fowler
We previously showed that chromosome 8 of A/J mice was associated with susceptibility to S. aureus infection. However, the specific genes responsible for this susceptibility are unknown. Chromosome substitution strain 8 (CSS8) mice, which have chromosome 8 from A/J but an otherwise C57BL/6J genome, were used to identify the genetic determinants of susceptibility to S. aureus on chromosome 8. Quantitative trait loci (QTL) mapping of S. aureus-infected N2 backcross mice (F1 [C8A] × C57BL/6J) identified a locus 83180780-88103009 (GRCm38/mm10) on A/J chromosome 8 that was linked to S...
2017: PloS One
https://www.readbyqxmd.com/read/28573328/human-cd200-suppresses-macrophage-mediated-xenogeneic-cytotoxicity-and-phagocytosis
#4
Rieko Sakai, Akira Maeda, Thuy-Vy Choi, Pei-Chi Lo, Patmika Jiaravuthiasan, Afifah Mod Shabri, Han-Tang Wang, Rei Matsuura, Tasuku Kodama, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
PURPOSE: Various strategies, such as the generation of alpha-1,3-galactosyltransferase knocked-out pigs and CD55 transgenic pigs, have been investigated to inhibit pig to human xenogeneic rejection. Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also that of cellular xenogeneic rejection (CXR). Although macrophages have been well known to play a critical role in CXR, monocyte/macrophage-mediated xenogeneic rejection has not been well studied...
June 1, 2017: Surgery Today
https://www.readbyqxmd.com/read/28547819/the-impact-of-serum-incubation-time-on-igm-igg-binding-to-porcine-aortic-endothelial-cells
#5
Zhongqiang Zhang, Bingsi Gao, Chengjiang Zhao, Cassandra Long, Haizhi Qi, Mohamed Ezzelarab, David Kc Cooper, Hidetaka Hara
The results of the assay for measuring anti-non-Gal antibodies (which affect pig xenograft survival) in recipients are important. Serum incubation time and concentration may be important factors in the extent of antibody binding to the graft. The aim of this in vitro study was to determine the optimal incubation time and serum concentration for measuring anti-non-Gal antibody binding to porcine aortic endothelial cells (pAECs). Pooled human, naive, and sensitized baboon sera were incubated with wild-type, α1,3-galactosyltransferase gene-knockout (GTKO), and GTKO/human CD55 pAECs...
May 25, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28542228/alteration-of-membrane-complement-regulators-is-associated-with-transporter-status-in-patients-on-peritoneal-dialysis
#6
Daniel Kitterer, Dagmar Biegger, Stephan Segerer, Niko Braun, M Dominik Alscher, Joerg Latus
INTRODUCTION: A growing body of evidence from animal models and cell culture studies indicate an important role of a local regulatory complement system (CS) in peritoneal injury during peritoneal dialysis (PD). We investigated the expression of the local regulatory CS (reflected by CD46,CD55,CD59) in the peritoneal tissue of patients with different membrane function characteristics. PATIENTS AND METHODS: Biopsies from the parietal peritoneum were taken from 24 patients on PD, 22 uremic patients prior to PD...
2017: PloS One
https://www.readbyqxmd.com/read/28516949/paroxysmal-nocturnal-haemoglobinuria
#7
REVIEW
Anita Hill, Amy E DeZern, Taroh Kinoshita, Robert A Brodsky
Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell (HSC) disease that presents with haemolytic anaemia, thrombosis and smooth muscle dystonias, as well as bone marrow failure in some cases. PNH is caused by somatic mutations in PIGA (which encodes phosphatidylinositol N-acetylglucosaminyltransferase subunit A) in one or more HSC clones. The gene product of PIGA is required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; thus, PIGA mutations lead to a deficiency of GPI-anchored proteins, such as complement decay-accelerating factor (also known as CD55) and CD59 glycoprotein (CD59), which are both complement inhibitors...
May 18, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28510725/ifitm3-tlr3-and-cd55-genes-snps-and-cumulative-ge-netic-risks-for-severe-outcomes-in-chinese-patients-with-h7n9-h1n1pdm09-influenza
#8
Nelson Lee, Bin Cao, Changwen Ke, Hongzhou Lu, Yunwen Hu, Ht Claudia Tam, Cw Ronald Ma, Dawei Guan, Zhaoqin Zhu, Hui Li, Lin Mulei, Rity Yk Wong, Irene Mh Yung, Tin-Nok Hung, Kirsty Kwok, Peter Horby, Sc David Hui, Cw Martin Chan, Ks Paul Chan
Background: We examined associations between SNPs (single-nucleotide-polymorphisms) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in Chinese patients. Methods: A multicenter-study was conducted on 275 adult cases of prospectively-diagnosed H7N9 and H1N1pdm09 infections. Host DNA was extracted from diagnostic respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4 rs4986790/4986791 were targeted for genotyping by Sanger-sequencing...
May 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28506571/tumor-necrosis-factor-receptor-associated-factor-traf-6-inhibition-mitigates-the-pro-inflammatory-roles-and-proliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#9
Lang-Jing Zhu, Tie-Cheng Yang, Qiang Wu, Li-Ping Yuan, Zhen-Wei Chen, Min-Hong Luo, Hai-Ou Zeng, Dong-Ling He, Cai-Ju Mo
BACKGROUND: Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) play a crucial role in RA through producing inflammatory cytokines and proteases which could cause cartilage destruction. We showed previously that elevated expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) in RA synovium correlated significantly with the severity of synovitis and the number of infiltrated inflammatory cells. The aims of this study are to detect the roles of TRAF6 in RA-FLSs...
May 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28500075/overexpression-of-human-cd55-and-cd59-or-treatment-with-human-cd55-protects-against-renal-ischemia-reperfusion-injury-in-mice
#10
Anjan K Bongoni, Bo Lu, Evelyn J Salvaris, Veena Roberts, Doreen Fang, Jennifer L McRae, Nella Fisicaro, Karen M Dwyer, Peter J Cowan
Deficiency in the membrane-bound complement regulators CD55 and CD59 exacerbates renal ischemia-reperfusion injury (IRI) in mouse models, but the effect of increasing CD55 and CD59 activity has not been examined. In this study, we investigated the impact of overexpression of human (h) CD55 ± hCD59 or treatment with soluble rhCD55 in a mouse model of renal IRI. Unilaterally nephrectomised mice were subjected to 18 (mild IRI) or 22 min (moderate IRI) warm renal ischemia, and analyzed 24 h after reperfusion for renal function (serum creatinine and urea), complement deposition (C3b/c and C9), and infiltration of neutrophils and macrophages...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28495852/high-throughput-mrna-sequencing-of-stromal-cells-from-endometriomas-and-endometrium
#11
Kadri Rekker, Merli Saare, Elo Eriste, Tõnis Tasa, Viktorija Kukuškina, Anne Mari Roost, Kristi Anderson, Külli Samuel, Helle Karro, Andres Salumets, Maire Peters
The aetiology of endometriosis is still unclear and to find mechanisms behind the disease development it is important to study each cell type from endometrium and ectopic lesions independently. The objective of this study was to uncover complete mRNA profiles in uncultured stromal cells from paired samples of endometriomas and eutopic endometrium. High-throughput mRNA sequencing revealed over 1,300 dysregulated genes in stromal cells from ectopic lesions, including several novel genes in the context of endometriosis...
May 11, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28474373/angiopoietin-1-and-angiopoietin-2-protect-porcine-iliac-endothelial-cells-from-human-antibody-mediated-complement-dependent-cytotoxicity-through-phosphatidylinositide-3-kinase-akt-pathway-activation
#12
Hanchao Gao, Pengfei Chen, Ling Wei, Jia Xu, Lu Liu, Yanli Zhao, Hidetaka Hara, Dengke Pan, Zesong Li, David K C Cooper, Zhiming Cai, Lisha Mou
Cytokines play crucial roles in inflammation, but their role in xenotransplantation remains elusive. We assessed the role of several cytokines using an in vitro model of human antibody-mediated complement-dependent cytotoxicity (CDC). Recombinant human angiopoietin-1 (Ang-1) protected porcine iliac endothelial cells (PIECs) from human antibody-mediated CDC. Interestingly, human angiopoietin-2 (Ang-2) had a similar protective effect on PIECs. By flow cytometry analysis, the extent of human IgM and IgG binding to PIECs did not decrease when PIECs were exposed to Ang-1/Ang-2...
May 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28429508/immunophenotyping-and-activation-status-of-maternal-peripheral-blood-leukocytes-during-pregnancy-and-labour-both-term-and-preterm
#13
Jianhong Zhang, Oksana Shynlova, Sally Sabra, Annie Bang, Laurent Briollais, Stephen J Lye
The onset of labour in rodents and in humans is associated with physiological inflammation which is manifested by infiltration of activated maternal peripheral leukocytes (mPLs) into uterine tissues. Here, we used flow cytometry to immunophenotype mPLs throughout gestation and labour, both term and preterm. Peripheral blood was collected from non-pregnant women and pregnant women in the 1st, 2nd and 3rd trimesters. Samples were also collected from women in active labour at term (TL) or preterm (PTL) and compared with women term not-in-labour (TNIL) and preterm not-in-labour (PTNIL)...
April 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28405609/preconditioned-mesenchymal-stem-cells-treat-myasthenia-gravis-in-a-humanized-preclinical-model
#14
Muriel Sudres, Marie Maurer, Marieke Robinet, Jacky Bismuth, Frédérique Truffault, Diane Girard, Nadine Dragin, Mohamed Attia, Elie Fadel, Nicola Santelmo, Camille Sicsic, Talma Brenner, Sonia Berrih-Aknin
Myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) Abs is an autoimmune disease characterized by severe defects in immune regulation and thymic inflammation. Because mesenchymal stem cells (MSCs) display immunomodulatory features, we investigated whether and how in vitro-preconditioned human MSCs (cMSCs) could treat MG disease. We developed a new humanized preclinical model by subcutaneously grafting thymic MG fragments into immunodeficient NSG mice (NSG-MG model). Ninety percent of the animals displayed human anti-AChR Abs in the serum, and 50% of the animals displayed MG-like symptoms that correlated with the loss of AChR at the muscle endplates...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28399943/bipolar-disorder-patients-display-reduced-serum-complement-levels-and-elevated-peripheral-blood-complement-expression-levels
#15
Uğur Akcan, Sercan Karabulut, Cem İsmail Küçükali, Sibel Çakır, Erdem Tüzün
OBJECTIVE: Bipolar disorder (BD) patients have recently been shown to exhibit increased proinflammatory cytokine levels indicating the role of inflammation in this disease. As inflammatory responses often include complement level alterations and complement production is influenced by cytokines, we aimed to find out whether complement system is activated in BD in a time-dependent manner and complement factors are involved in BD pathogenesis. METHODS: Serum C4, factor B, sC5b-9 and neuron-specific enolase levels were measured by enzyme-linked immunosorbent assay, whereas peripheral blood mononuclear cell messenger RNA (mRNA) expression levels of C1q, C4, factor B and CD55 were measured by real-time polymerase chain reaction in chronic BD patients (n=22), first episode BD patients (n=24) and healthy controls (n=19)...
April 12, 2017: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/28345461/expression-and-prognostic-value-of-soluble-cd97-and-its-ligand-cd55-in-intrahepatic-cholangiocarcinoma
#16
Ze-Wu Meng, Min-Chao Liu, Hai-Jie Hong, Qiang Du, Yan-Ling Chen
The incidence rate of intrahepatic cholangiocarcinoma is rising, and treatment options are limited. Therefore, new biological markers of intrahepatic cholangiocarcinoma are needed. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to analyze the expressions of CD97, CD55, and soluble CD97 in 71 patients with intrahepatic cholangiocarcinoma and 10 patients with hepatolithiasis. CD97 and CD55 were not expressed in hepatolithiatic tissues, but positive expression was observed in 76.1% (54/71) and 70...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28303661/immunological-and-physiological-observations-in-baboons-with-life-supporting-genetically-engineered-pig-kidney-grafts
#17
Hayato Iwase, Hidetaka Hara, Mohamed Ezzelarab, Tao Li, Zhongqiang Zhang, Bingsi Gao, Hong Liu, Cassandra Long, Yi Wang, Amy Cassano, Edwin Klein, Carol Phelps, David Ayares, Abhinav Humar, Martin Wijkstrom, David K C Cooper
BACKGROUND: Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently. METHODS: Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28292372/clinico-haematological-features-of-paroxysmal-nocturnal-haemoglobinuria
#18
Maria Khan, Saqib Qayyum Ahmad, Mukarram Bashir, Parvez Ahmed, Muhammad Ayyub
The aim of this study was to determine the frequency of various clinico-haematological features in patients suffering from paroxysmal nocturnal haemoglobinuria (PNH). It was an observational study carried out from October 2008 - January 2016. All the patients of PNH, diagnosed on the basis of clinical and laboratory findings and confirmed by CD55 and CD59 deficiency on red cells by means of flow cytometry, were included in the study. A total of 22 patients were diagnosed which included 18 (81.8%) males and 4 (18...
January 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28140725/complement-dependent-cytotoxicity-induced-by-therapeutic-antibodies-in-b-cell-acute-lymphoblastic-leukemia-is-dictated-by-target-antigen-expression-levels-and-augmented-by-loss-of-membrane-bound-complement-inhibitors
#19
Floris C Loeff, H M Esther van Egmond, Bart A Nijmeijer, J H Frederik Falkenburg, Constantijn J Halkes, Inge Jedema
To optimally utilize therapeutic monoclonal antibodies in the treatment of B-cell acute lymphoblastic leukemia (B-ALL) understanding their mechanisms of action and the factors influencing these mechanisms is required. We show strong correlations between target antigen expression levels and sensitivity to complement-dependent cytotoxicity (CDC) induced by rituximab, ofatumumab, or alemtuzumab in a panel of cell lines derived from primary B-ALL cells and in primary B-ALL samples. Simultaneous loss of expression of membrane-bound complement regulatory proteins (mCRP) CD55 and CD59 due to glycophosphatidylinositol-anchor deficiency, significantly increased sensitivity to CDC...
September 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28104671/lack-of-association-of-cd55-receptor-genetic-variants-and-severe-malaria-in-ghanaian-children
#20
Kathrin Schuldt, Christa Ehmen, Juergen Sievertsen, Jennifer Evans, Juergen May, Daniel Ansong, Birgit Muntau, Gerd Ruge, Christian Timmann, Tsiri Agbenyega, Rolf D Horstmann, Thorsten Thye
In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by Plasmodium falciparum, the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM) susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human CD55 gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes...
March 10, 2017: G3: Genes—Genomes—Genetics
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