The Experts below are selected from a list of 1479 Experts worldwide ranked by ideXlab platform
Katarzyna Michalak - One of the best experts on this subject based on the ideXlab platform.
-
the role of complement activating collectins and associated serine proteases in patients with hematological malignancies receiving high dose chemotherapy and autologous hematopoietic stem cell transplantations auto hsct
Frontiers in Immunology, 2018Co-Authors: Anna S świerzko, Mateusz Michalski, Anna Sokolowska, Mateusz Nowicki, łukasz Eppa, Agnieszka Szalapoździej, Iwona Mitrus, Anna Szmigielskakaplon, M Sobczykkruszelnicka, Katarzyna MichalakAbstract:We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous haematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also one and/or three months post transplantation. The results were compared with data from 267 healthy controls and analysed in relation to clinical data to explore possible associations with cancer and with chemotherapy-induced medical complications. We found a higher frequency of MBL Deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients compared with controls. It was however not associated with hospital infections or post-HSCT recovery of leukocytes, but seemed to be associated with the most severe infections during follow-up. Paradoxically, high MBL serum levels were a risk factor for prolonged fever and some infections. The first possible association of MBL2 gene 3’-untranslated region polymorphism with cancer (lymphoma) in Caucasians was noted. Heterozygosity for MASP2 gene +359 A>G mutation was relatively frequent in lymphoma patients who experienced bacteremia during hospital stay. The median concentration of CL-LK was higher in myeloma patients compared with healthy subjects. Chemotherapy induced marked increases in serum MBL and MASP-2 concentrations, prolonged for several weeks and relatively slighter decline in CL-LK level within one week. Conflicting findings on the influence of MBL on infections following chemotherapy of myeloma and lymphoma have been reported. Here we found no evidence for an association between MBL Deficiency and infection during the short period of neutropenia following conditioning treatment before HSCT. However, we noted a possible protective effect of MBL during follow-up, and suspected that to be fully effective when able to act in combination with phagocytic cells after their recovery.
-
The Role of Complement Activating Collectins and Associated Serine Proteases in Patients With Hematological Malignancies, Receiving High-Dose Chemotherapy, and Autologous Hematopoietic Stem Cell Transplantations (Auto-HSCT)
'Frontiers Media SA', 2018Co-Authors: Anna S. Świerzko, Mateusz Michalski, Mateusz Nowicki, łukasz Eppa, Iwona Mitrus, Anna Sokołowska, Agnieszka Szala-poździej, Anna Szmigielska-kapłon, Małgorzata Sobczyk-kruszelnicka, Katarzyna MichalakAbstract:We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also 1 and/or 3 months post transplantation. The results were compared with data from 267 healthy controls and analyzed in relation to clinical data to explore possible associations with cancer and with chemotherapy-induced medical complications. We found a higher frequency of MBL Deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients compared with controls. It was however not associated with hospital infections or post-HSCT recovery of leukocytes, but seemed to be associated with the most severe infections during follow-up. Paradoxically, high MBL serum levels were a risk factor for prolonged fever and some infections. The first possible association of MBL2 gene 3′-untranslated region polymorphism with cancer (lymphoma) in Caucasians was noted. Heterozygosity for MASP2 gene +359 A>G mutation was relatively frequent in lymphoma patients who experienced bacteremia during hospital stay. The median concentration of CL-LK was higher in myeloma patients compared with healthy subjects. Chemotherapy induced marked increases in serum MBL and MASP-2 concentrations, prolonged for several weeks and relatively slighter decline in CL-LK level within 1 week. Conflicting findings on the influence of MBL on infections following chemotherapy of myeloma and lymphoma have been reported. Here we found no evidence for an association between MBL Deficiency and infection during the short period of neutropenia following conditioning treatment before HSCT. However, we noted a possible protective effect of MBL during follow-up, and suspected that to be fully effective when able to act in combination with phagocytic cells after their recovery
-
Data_Sheet_1_The Role of Complement Activating Collectins and Associated Serine Proteases in Patients With Hematological Malignancies, Receiving High-Dose Chemotherapy, and Autologous Hematopoietic Stem Cell Transplantations (Auto-HSCT).docx
2018Co-Authors: Anna S. Świerzko, Mateusz Michalski, Mateusz Nowicki, łukasz Eppa, Iwona Mitrus, Anna Sokołowska, Agnieszka Szala-poździej, Anna Szmigielska-kapłon, Małgorzata Sobczyk-kruszelnicka, Katarzyna MichalakAbstract:We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also 1 and/or 3 months post transplantation. The results were compared with data from 267 healthy controls and analyzed in relation to clinical data to explore possible associations with cancer and with chemotherapy-induced medical complications. We found a higher frequency of MBL Deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients compared with controls. It was however not associated with hospital infections or post-HSCT recovery of leukocytes, but seemed to be associated with the most severe infections during follow-up. Paradoxically, high MBL serum levels were a risk factor for prolonged fever and some infections. The first possible association of MBL2 gene 3′-untranslated region polymorphism with cancer (lymphoma) in Caucasians was noted. Heterozygosity for MASP2 gene +359 A>G mutation was relatively frequent in lymphoma patients who experienced bacteremia during hospital stay. The median concentration of CL-LK was higher in myeloma patients compared with healthy subjects. Chemotherapy induced marked increases in serum MBL and MASP-2 concentrations, prolonged for several weeks and relatively slighter decline in CL-LK level within 1 week. Conflicting findings on the influence of MBL on infections following chemotherapy of myeloma and lymphoma have been reported. Here we found no evidence for an association between MBL Deficiency and infection during the short period of neutropenia following conditioning treatment before HSCT. However, we noted a possible protective effect of MBL during follow-up, and suspected that to be fully effective when able to act in combination with phagocytic cells after their recovery.
Steffen Thiel - One of the best experts on this subject based on the ideXlab platform.
-
bipolar and panic disorders may be associated with hereditary defects in the innate immune system
Journal of Affective Disorders, 2014Co-Authors: Steffen Thiel, Rudi Steffensen, Jens C. Jensenius, Leslie Foldager, Ole Kohler, Ann Suhl Kristensen, Ole MorsAbstract:Abstract Background Mannan-binding lectin (MBL) and mannan-binding lectin-associated serine protease-2 (MASP-2) represent important arms of the innate immune system, and different deficiencies may result in infections or autoimmune diseases. Both bipolar and panic disorders are associated with increased inflammatory response, infections and mutual comorbidity. However, associations with MBL, MASP-2 or the gene, MBL2, coding for MBL, have not been investigated thoroughly. Methods One hundred patients with bipolar disorder, 100 with panic disorder and 349 controls were included. Serum concentrations of MBL and MASP-2 were measured and seven single nucleotide polymorphisms (SNPs) influencing these concentrations were genotyped. Disease association with genetic markers and serum levels were investigated. Results In panic disorder, we observed a large proportion (30%) of MBL deficient ( Limitations No information on course or severity of disorders was included, and only MBL and MASP-2 were measured, excluding other components from the complement pathway. Restrictions defined by ethnical committees preclude information of control׳s ethnic origin. Conclusions Significant differences in MBL and MASP-2 concentrations were observed between cohorts, especially an intriguing finding associating panic disorder with MBL Deficiency. These differences could not be fully explained by allele or haplotype frequency variations. Since MBL Deficiency is highly heterogeneous and associated with both infectious and autoimmune states, more research is needed to identify which complement pathway components could be associated with bipolar respectively panic disorder.
-
congenital h ficolin Deficiency in premature infants with severe necrotising enterocolitis
Gut, 2011Co-Authors: Luregn J Schlapbach, Steffen Thiel, Ulf Kessler, Roland A Ammann, Christoph Aebi, Jens C. JenseniusAbstract:In a recent issue of Gut , Muller et al reported on excessive colitis in a murine model of mannan-binding lectin (MBL) Deficiency.1 They showed that absence of MBL can lead to uncontrolled intestinal inflammation detrimental to the host. MBL is a pattern-recognition molecule activating the complement system by the lectin pathway. H-ficolin is structurally closely related to MBL and can activate the lectin pathway of complement independently of MBL. While low levels of MBL occur in 10% of Caucasians, H-ficolin Deficiency is extremely rare: studies involving over 100 000 adults found no case of H-ficolin Deficiency, suggesting it exerts crucial functions for the human immune system.2 The first report on the so far only patient diagnosed with H-ficolin Deficiency was published only recently,3 describing a patient with repeated infections who presented …
-
lack of the pattern recognition molecule mannose binding lectin increases susceptibility to influenza a virus infection
BMC Immunology, 2010Co-Authors: Weichuan Chang, Steffen Thiel, Mitchell R White, Patience Moyo, Sheree Mcclear, Kevan L Hartshorn, Kazue TakahashiAbstract:Background Mannose-binding lectin (MBL), a pattern recognition innate immune molecule, inhibits influenza A virus infection in vitro. MBL Deficiency due to gene polymorphism in humans has been associated with infection susceptibility. These clinical observations were confirmed by animal model studies, in which mice genetically lacking MBL were susceptible to certain pathogens, including herpes simplex virus 2.
-
the mannan binding lectin pathway and lung disease in cystic fibrosis dysfunction of mannan binding lectin associated serine protease 2 masp 2 may be a major modifier
Clinical Immunology, 2006Co-Authors: H.v. Olesen, Steffen Thiel, Rudi Steffensen, Jens Christian Jensenius, Peter Oluf SchiøtzAbstract:The lectin pathway of complement activation is initiated by mannan-binding lectin (MBL) or the ficolins through the common MBL-associated serine protease-2 (MASP-2). Deficiency of MBL has been associated with poorer outcome in cystic fibrosis (CF). We investigated the MBL pathway further by analysis of the MASP-2 Deficiency mutation (D105G) as well as MBL-2 genotypes. Concentrations and genotypes of MASP-2 and MBL in 109 CF patients were correlated to lung function and chronic infections. We describe the first CF patient homozygous for the mutation, a girl with extremely severe lung disease with no other precipitating factors. We suspect total MASP-2 dysfunction to be a major modifier of CF lung disease. However, heterozygosity for the D105G mutation of MASP-2 had no correlation to MBL pathway function or poor lung function. Lung function was higher in the MBL Deficiency determining genotypes (XA/YO+YO/YO) than in the other genotypes.
-
Deficiency of the mannan binding lectin pathway of complement and poor outcome in cystic fibrosis bacterial colonization may be decisive for a relationship
Clinical and Experimental Immunology, 2005Co-Authors: Malin Carlsson, Steffen Thiel, Jens Christian Jensenius, A G Sjoholm, Leif Eriksson, Marten Segelmark, Lennart TruedssonAbstract:In cystic fibrosis (CF) prognosis concerning lung damage development is highly variable and difficult to predict. Mannan-binding lectin (MBL) Deficiency has been reported to be associated with poor outcome in CF lung disease. MBL is a recognition molecule of the MBL pathway of the complement system and is encoded by a gene characterized by a high degree of polymorphism. Some genotypes result in low serum concentrations of MBL. MBL-associated serine protease 2 (MASP-2) is another protein belonging to the MBL pathway. A mutation resulting in low levels of MASP-2 in serum has been described recently. In the present study, 112 CF patients aged 4-54 years were investigated for MBL and MASP-2 genotypes, serum levels of MBL and MASP-2 and the MBL pathway function in serum. No correlation to reduced lung function or need for lung transplantation was seen, either for MBL Deficiency, MASP-2 gene mutation or reduced MBL pathway function. However, in the 27 patients colonized with Staphylococcus aureus, MBL-deficient genotypes were associated with decreased lung function. As expected, MBL pathway function in serum was reduced both in MBL-deficient patients and in patients carrying a mutant MASP-2 allele. An unexpected finding was that CF patients had higher serum levels of MBL than healthy controls when corrected for MBL genotype. In conclusion, MBL pathway function was affected both by MBL and by MASP-2 genotypes. However, MBL or MASP-2 levels in serum did not affect the clinical outcome in the cohort of CF patients studied.
Chantal Dumestreperard - One of the best experts on this subject based on the ideXlab platform.
-
phospholipase a2 receptor related membranous nephropathy and mannan binding lectin Deficiency
Journal of The American Society of Nephrology, 2016Co-Authors: Stephane Bally, Denise Ponard, Julien Faure, John Rendu, Frédérique Dijoud, Hanna Debiec, Pierre Ronco, Chantal DumestreperardAbstract:Most patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies against phospholipase A2 receptor (PLA2R). C3 and C5b-9 are found in immune deposits of IMN kidney biopsy specimens, but the pathway of complement activation in IMN remains elusive. We report the case of a patient who developed IMN with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1. Measurement of mannan binding lectin (MBL) antigenic level and activity revealed MBL Deficiency. Genotyping revealed a heterozygous (A/C) polymorphism in codon 57 of MBL2 exon 1 associated with homozygous and heterozygous variations in the promoter region at -550 (L/L) and -221 (X/Y), respectively, suggesting that the patient harbored the LXA/LYC haplotypes linked to MBL Deficiency. Genetic sequencing in 77 consecutive patients with IMN identified four patients with MBL2 promoter and coding region variations associated with MBL Deficiency and the same complement pattern in immune deposits as the index patient. In contrast, patients with wild-type MBL2 had immune deposits with intense Cd4 staining. Thus, IMN can develop in patients with complete MBL Deficiency, with complement activated mainly by the alternative pathway, whereas the lectin pathway is also activated in those with wild-type MBL2.
Pierre Ronco - One of the best experts on this subject based on the ideXlab platform.
-
phospholipase a2 receptor related membranous nephropathy and mannan binding lectin Deficiency
Journal of The American Society of Nephrology, 2016Co-Authors: Stephane Bally, Denise Ponard, Julien Faure, John Rendu, Frédérique Dijoud, Hanna Debiec, Pierre Ronco, Chantal DumestreperardAbstract:Most patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies against phospholipase A2 receptor (PLA2R). C3 and C5b-9 are found in immune deposits of IMN kidney biopsy specimens, but the pathway of complement activation in IMN remains elusive. We report the case of a patient who developed IMN with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1. Measurement of mannan binding lectin (MBL) antigenic level and activity revealed MBL Deficiency. Genotyping revealed a heterozygous (A/C) polymorphism in codon 57 of MBL2 exon 1 associated with homozygous and heterozygous variations in the promoter region at -550 (L/L) and -221 (X/Y), respectively, suggesting that the patient harbored the LXA/LYC haplotypes linked to MBL Deficiency. Genetic sequencing in 77 consecutive patients with IMN identified four patients with MBL2 promoter and coding region variations associated with MBL Deficiency and the same complement pattern in immune deposits as the index patient. In contrast, patients with wild-type MBL2 had immune deposits with intense Cd4 staining. Thus, IMN can develop in patients with complete MBL Deficiency, with complement activated mainly by the alternative pathway, whereas the lectin pathway is also activated in those with wild-type MBL2.
Hanna Debiec - One of the best experts on this subject based on the ideXlab platform.
-
phospholipase a2 receptor related membranous nephropathy and mannan binding lectin Deficiency
Journal of The American Society of Nephrology, 2016Co-Authors: Stephane Bally, Denise Ponard, Julien Faure, John Rendu, Frédérique Dijoud, Hanna Debiec, Pierre Ronco, Chantal DumestreperardAbstract:Most patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies against phospholipase A2 receptor (PLA2R). C3 and C5b-9 are found in immune deposits of IMN kidney biopsy specimens, but the pathway of complement activation in IMN remains elusive. We report the case of a patient who developed IMN with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1. Measurement of mannan binding lectin (MBL) antigenic level and activity revealed MBL Deficiency. Genotyping revealed a heterozygous (A/C) polymorphism in codon 57 of MBL2 exon 1 associated with homozygous and heterozygous variations in the promoter region at -550 (L/L) and -221 (X/Y), respectively, suggesting that the patient harbored the LXA/LYC haplotypes linked to MBL Deficiency. Genetic sequencing in 77 consecutive patients with IMN identified four patients with MBL2 promoter and coding region variations associated with MBL Deficiency and the same complement pattern in immune deposits as the index patient. In contrast, patients with wild-type MBL2 had immune deposits with intense Cd4 staining. Thus, IMN can develop in patients with complete MBL Deficiency, with complement activated mainly by the alternative pathway, whereas the lectin pathway is also activated in those with wild-type MBL2.