58 research outputs found
Open ADAMTS13 conformation in immune-mediated thrombotic thrombocytopenic purpura is induced by anti- ADAMTS13 autoantibodies and corresponds with an ongoing ADAMTS13 pathology
No full textstatus: Accepte
Poster Session 2 - Workshop Rodent-Borne Diseases
No full text62 Schistosomiasis in the Senegal River Basin and the role of wild rodents as reservoir hosts Stefano Catalano, Elsa Léger, Cheikh B. Fall, Anna Borlase, Mariama Sène, Nicolas D. Diouf, Khalilou Bâ, Joanne P. Webster
63 Rodents diversity and pathogen carriage at Limpopo National Park villages, Mozambique Iara Gomes-Jaintilal, Cristiane Silveira, José Fafetine, Luís Neves
64 Mice in and around the city of Utrecht, The Netherlands, are carriers of Clostridium difficile but not ESBL-producing Enterobacteriaceae, Salmonella spp. or MRSA Céline Harmanus, Sara A. Burt
65 Detection of Rickettsia pathogens in small rodents and their ectoparasites in Lithuania Evelina Kaminskienė, Dalytė Mardosaitė-Busaitienė, Algimantas Paulauskas, Jana Radzijevskaja, Indrė Lipatova, Linas Balčiauskas
66 Detection of Leptospira and seasonal prevalence of fleas collected from rodents in Mukwe Constituency, Kavango-East Region of Namibia Saima Kapia, Seth J. Eiseb, Loth S. Mulungu, Pablo Tortosa, Steven R. Belmain
67 Rodents from a rice milling station in Bangladesh infected with Toxoplasma gondii Inge M. Krijger, Jan B.W.J. Cornelissen, Steven R. Belmain, Bastiaan G. Meerburg
68 Leptospirosis and toxoplasmosis in wild rodents in The Netherlands Inge M. Krijger, Marga G. A. Goris, Ahmed A. Ahmed, Peter W.G. Groot Koerkamp, Bastiaan G. Meerburg
69 Leptospirosis in rodents in peri-urban Bangladesh Inge M. Krijger, Ahmed A. Ahmed, Marga G.A. Goris, Peter W.G. Groot Koerkamp, Bastiaan G. Meerburg
70 Detection of Bartonella spp. in red squirrel (Sciurus vulgaris) and their ectoparasites in Lithuania Indrė Lipatova, Irma Ražanskė, Algimantas Paulauskas
71 Genetic diversity of Bartonella strains in small rodents Dalytė Mardosaitė-Busaitienė, Jana Radzijevskaja, Algimantas Paulauskas, Linas Balčiauskas, Maksim Bračikov
72 Resistance to last-resort human antimicrobial agents among gram-negative bacteria recovered from Barcelona Norway rats (Rattus norvegicus) Marta Marí-Almirall, Yaiza Vallejo, Sara Sabaté, Sandra Franco, Laura Muñoz, Maria Nieto , Clara Cosgaya, Jordi Pascual, Ignasi Roca, Tomás Montalvo
73 Evaluation of rodent control to fight Lassa fever through mathematical modelling Joachim Mariën, Herwig Leirs, N’Faly Magassouba, Elisabeth Fichet-Calvet
74 Responses of rodent reservoirs of zoonotic diseases to anthropogenic land-use change: a meta-analysis Hugo Mendoza, André V. Rubio, Gabriel E. García-Peñ, Gerardo Suzan, Javier A. Simonetti
75 First bacteriological screening of Norway rats, Rattus norvegicus, in Barcelona (Spain) Tomás Montalvo, Jordi Vila, Sara Sabaté, Beatriz Ramírez, Raquel Planell, Mikel Martínez, Aida Peiró, Jordi Pascual, Sandra Franco, Víctor Peracho
76 Education in health associated with gamification against leptospirosis Isa B. Neves, Ricardo Lustosa, Patricia Brito, Hussein Khalil, Federico Costa, Michael Begon
77 No role for rodents as alternative hosts for cutaneous leishmaniasis in S. Ethiopia Myrthe Pareyn, Girma Negatu, Massebo Fekadu, Simon Shibru, Herwig Leirs
78 Puumala hantavirus dynamics in bank voles: identification of environmental correlates to predict human infection risk Daniela Reil,, Christian Imholt, Ulrike M. Rosenfeld, Sabrina Schmidt, Rainer G. Ulrich, Jana A. Eccard, Jens Jacob
79 Survey on zoonotic helminthiases in Norway rats, Rattus norvegicus, from the city of Barcelona Joan Sanxis,, M. Teresa Galán-Puchades, Jordi Pascual, Rubén Bueno-Marí, Sandra Franco, Víctor Peracho, Tomás Montalvo,, Màrius V. Fuentes62 Schistosomiasis in the Senegal River Basin and the role of wild rodents as reservoir hosts Stefano Catalano, Elsa Léger, Cheikh B. Fall, Anna Borlase, Mariama Sène, Nicolas D. Diouf, Khalilou Bâ, Joanne P. Webster
63 Rodents diversity and pathogen carriage at Limpopo National Park villages, Mozambique Iara Gomes-Jaintilal, Cristiane Silveira, José Fafetine, Luís Neves
64 Mice in and around the city of Utrecht, The Netherlands, are carriers of Clostridium difficile but not ESBL-producing Enterobacteriaceae, Salmonella spp. or MRSA Céline Harmanus, Sara A. Burt
65 Detection of Rickettsia pathogens in small rodents and their ectoparasites in Lithuania Evelina Kaminskienė, Dalytė Mardosaitė-Busaitienė, Algimantas Paulauskas, Jana Radzijevskaja, Indrė Lipatova, Linas Balčiauskas
66 Detection of Leptospira and seasonal prevalence of fleas collected from rodents in Mukwe Constituency, Kavango-East Region of Namibia Saima Kapia, Seth J. Eiseb, Loth S. Mulungu, Pablo Tortosa, Steven R. Belmain
67 Rodents from a rice milling station in Bangladesh infected with Toxoplasma gondii Inge M. Krijger, Jan B.W.J. Cornelissen, Steven R. Belmain, Bastiaan G. Meerburg
68 Leptospirosis and toxoplasmosis in wild rodents in The Netherlands Inge M. Krijger, Marga G. A. Goris, Ahmed A. Ahmed, Peter W.G. Groot Koerkamp, Bastiaan G. Meerburg
69 Leptospirosis in rodents in peri-urban Bangladesh Inge M. Krijger, Ahmed A. Ahmed, Marga G.A. Goris, Peter W.G. Groot Koerkamp, Bastiaan G. Meerburg
70 Detection of Bartonella spp. in red squirrel (Sciurus vulgaris) and their ectoparasites in Lithuania Indrė Lipatova, Irma Ražanskė, Algimantas Paulauskas
71 Genetic diversity of Bartonella strains in small rodents Dalytė Mardosaitė-Busaitienė, Jana Radzijevskaja, Algimantas Paulauskas, Linas Balčiauskas, Maksim Bračikov
72 Resistance to last-resort human antimicrobial agents among gram-negative bacteria recovered from Barcelona Norway rats (Rattus norvegicus) Marta Marí-Almirall, Yaiza Vallejo, Sara Sabaté, Sandra Franco, Laura Muñoz, Maria Nieto , Clara Cosgaya, Jordi Pascual, Ignasi Roca, Tomás Montalvo
73 Evaluation of rodent control to fight Lassa fever through mathematical modelling Joachim Mariën, Herwig Leirs, N’Faly Magassouba, Elisabeth Fichet-Calvet
74 Responses of rodent reservoirs of zoonotic diseases to anthropogenic land-use change: a meta-analysis Hugo Mendoza, André V. Rubio, Gabriel E. García-Peñ, Gerardo Suzan, Javier A. Simonetti
75 First bacteriological screening of Norway rats, Rattus norvegicus, in Barcelona (Spain) Tomás Montalvo, Jordi Vila, Sara Sabaté, Beatriz Ramírez, Raquel Planell, Mikel Martínez, Aida Peiró, Jordi Pascual, Sandra Franco, Víctor Peracho
76 Education in health associated with gamification against leptospirosis Isa B. Neves, Ricardo Lustosa, Patricia Brito, Hussein Khalil, Federico Costa, Michael Begon
77 No role for rodents as alternative hosts for cutaneous leishmaniasis in S. Ethiopia Myrthe Pareyn, Girma Negatu, Massebo Fekadu, Simon Shibru, Herwig Leirs
78 Puumala hantavirus dynamics in bank voles: identification of environmental correlates to predict human infection risk Daniela Reil,, Christian Imholt, Ulrike M. Rosenfeld, Sabrina Schmidt, Rainer G. Ulrich, Jana A. Eccard, Jens Jacob
79 Survey on zoonotic helminthiases in Norway rats, Rattus norvegicus, from the city of Barcelona Joan Sanxis,, M. Teresa Galán-Puchades, Jordi Pascual, Rubén Bueno-Marí, Sandra Franco, Víctor Peracho, Tomás Montalvo,, Màrius V. Fuente
Generation of anti-idiotypic antibodies to detect anti-spacer antibody idiotopes in acute thrombotic thrombocytopenic purpura patients
No full textIn autoantibody-mediated autoimmune diseases, autoantibody profiling allows to stratify patients and link autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura patients, stratification according to antibody profiles and their clinical relevance has not been fully explored. We aimed at developing a new type of autoantibody profiling assay for immune-mediated thrombotic thrombocytopenic purpura based on the use of anti-idiotypic antibodies. Anti-idiotypic antibodies against 3 anti-spacer autoantibodies were generated in mice and were used to capture the respective anti-spacer idiotopes from 151 acute immune-mediated thrombotic thrombocytopenic purpura plasma samples. We next deciphered these anti-spacer idiotope profiles in immune-mediated thrombotic thrombocytopenic purpura patients and investigated if these limited idiotope profiles could be linked with disease severity. We developed 3 anti-idiotypic antibodies that recognized particular idiotopes in the anti-spacer autoantibodies II-1, TTP73 or I-9, that are involved in ADAMTS13 binding. Thirty-five, 24 and 42% of patients were positive for antibodies with the II-1, TTP73 and I-9 idiotopes, respectively. Stratifying patients according to the corresponding 8 anti-spacer idiotope profiles revealed an until now unknown insight into the anti-spacer II-1, TTP73 and I-9 idiotope profiles in these patients. Finally, these limited idiotope profiles showed no association with disease severity. We successfully developed 3 anti-idiotypic antibodies that allowed us to determine the profiles of the anti-spacer II-1, TTP73 and I-9 idiotopes in immune-mediated thrombotic thrombocytopenic purpura patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow to identify idiotope profiles of clinical, prognostic value
Shielding of the A1 domain by the D'D3 domains of von Willebrand factor modulates its interaction with platelet glycoprotein Ib-IX-V
No full textSoluble von Willebrand factor (VWF) has a low affinity for platelet glycoprotein (GP) Ibalpha and needs immobilization and/or high shear stress to enable binding of its A1 domain to the receptor. The previously described anti-VWF monoclonal antibody 1C1E7 enhances VWF/GPIbalpha binding and recognizes an epitope in the amino acids 764-1035 region in the N-terminal D'D3 domains. In this study we demonstrated that the D'D3 region negatively modulates the VWF/GPIb-IX-V interaction; (i) deletion of the D'D3 region in VWF augmented binding to GPIbalpha, suggesting an inhibitory role for this region, (ii) the isolated D'D3 region inhibited the GPIbalpha interaction of a VWF deletion mutant lacking this region, indicating that intramolecular interactions limit the accessibility of the A1 domain, (iii) using a panel of anti-VWF monoclonal antibodies, we next showed that the D'D3 region is in close proximity with the A1 domain in soluble VWF but not when VWF was immobilized; (iv) destroying the epitope of 1C1E7 resulted in a mutant VWF with an increased affinity for GPIbalpha. Our results support a model of domain translocation in VWF that allows interaction with GPIbalpha. The suggested shielding interaction of the A1 domain by the D'D3 region then becomes disrupted by VWF immobilization.status: Publishe
False positive results in chimeraplasty for von Willebrand Disease
No full textChimeraplasty or the use of chimeric RNA/DNA oligonucleotides (RDOs) to correct single-base mutations emerged in the field of gene therapy with reported base pair conversions of up to 40%. We investigated the applicability of chimeraplasty to correct a point mutation in the von Willebrand Factor (VWF) gene resulting in a von Willebrand Disease (VWD) type 3 phenotype. Although we have access to VWD type 3 dogs, we used wild type endothelial cells for in vitro studies, as isolation of endothelial cells from VWD type 3 dogs is not straightforward due to the bleeding diathesis. RDOs to convert the wild type VWF gene into VWD type 3 gDNA were constructed and used in various transfection conditions. However, no gene conversion could be detected either in the RNA or in the DNA isolated from transfected cells, not even with the sensitive colony hybridisation technique, despite the presence of RDOs in the cell nucleus. On the other hand, sequence analysis of isolated DNA of transfected cells did reveal the presence of VWF type 3 DNA. However, this apparent conversion is very likely not the result of RDO-mediated nucleotide conversion as the same VWF type 3 DNA sequence was also detected in negative control experiments where no RDO was used.status: Publishe
Plasma glycocalicin as a source of GPIbalpha in the von Willebrand factor ristocetin cofactor ELISA
No full textWe have previously demonstrated that the von Willebrand factor ristocetin cofactor activity (VWF:RCo), used in the diagnosis of vonWillebrand disease (VWD), can be accurately determined via ELISA by measuring the ristocetin-induced binding of VWF to a captured recombinant fragment of GPIbalpha (rfGPIbalpha, AA 1-289) (Vanhoorelbeke et al., Thromb Haemost 2000; 83: 107-13). This ELISA is more reliable than the currently used platelet agglutination test. Normal plasma contains relatively high concentrations of glycocalicin, a proteolytic fragment of GPIbalpha. We therefore studied whether non-purified plasma glycocalicin can replace rfGPIbalpha in our ELISA. Of 42 anti-GPIbalpha monoclonal antibodies (MAbs) capable of binding plasma glycocalicin, only one MAb captured glycocalicin in a spatial orientation exposing the VWF-binding site in glycocalicin, allowing a specific and dose-dependent ristocetin-mediated VWF-binding. Intra- and interassay variability were comparable with those for the rfGPIbalpha based VWF:RCo ELISA. The VWF:RCo activity of plasma from 33 normal individuals, 19 type 1, 16 type 2A, 9 type 2B, 8 type 2M and 7 type 3VWD patients was determined with this ELISA and allowed a clear identification of VWD patients. Furthermore, determination of the VWF:RCo/VWF:Ag ratio resulted in the discrimination between type 1 and type 2 VWD patients. Results for the glycocalicin based and the rfGPIbalpha based VWF:RCo ELISAs were in good agreement (r=0.943). There was also a good correlation between the glycocalicin based ELISA and the standard platelet agglutination test (r=0.963). In conclusion, to diagnose VWD, a VWF:RCo ELISA based on antibody immobilized plasma glycocalicin can be performed reliably.sponsorship: ‘Fonds voor Wetenschappelijk Onderzoek Vlaanderen’status: Publishe
Shielding of the A1 domain by the D'D3 domains of von Willebrand factor modulates its interaction with platelet glycoprotein Ib-IX-V
No full text
Rational humanization of the powerful antithrombotic anti-GPIb alpha antibody: 6B4
No full textFab-fragments of the monoclonal antibody 6134, raised against human glycoprotein lb alpha (GPIb alpha), have a powerful antithrombotic effect in baboons by blocking the GPIb alpha binding site for von Willebrand factor (VWF), without significant prolongation of the skin bleeding time. In order to bring this antibody to the clinic,we here humanized for the first time an anti-human GPIb alpha by variable-domain resurfacing guided by computer modeling. First, the genes coding for the variable regions of the heavy and light chains of 6134 were cloned and sequenced. Based on this, a three-dimensional structure of the Fv-fragment was constructed by using homology-based modeling, and with this and comparison with antibodies with known structure,"murine" putative immunogenic residues which are exposed, were changed for "human-like" residues. The humanized Fab-fragment, h6B4-Fab, was constructed in the pKaneo vector system, expressed and purified and showed in vitro an unaltered, even slightly higher binding affinity for its antigen than the murine form as determined by different ELISA set-ups and surface plasmon resonance. Finally, injection of doses of 0.1 to 1.5 mg/kg of h6B4-Fab in baboons showed that both pharmacokinetics and ex-vivo bio-activity of the molecule were to a large extent preserved. In conclusion,the method used hereto humanize 6134 by resurfacing resulted in a fully active derivative, which is now ready for further development.sponsorship: Flanders and South Africa|BIL/04/56, Instituut voor de Aanmoediging van Innovatie door Wetenschap en Technologie in Vlaanderen|IWT 020473status: Publishe
483. Phenotypic Correction of Von Willebrand Disease Type 3 Blood-Derived Endothelial Cells with Lentiviral Vectors Expressing Von Willebrand Factor
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