The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Jodi A Flaws - One of the best experts on this subject based on the ideXlab platform.
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tumor necrosis factor tnf receptor type 2 is an important mediator of tnf alpha function in the mouse ovary
Biology of Reproduction, 2007Co-Authors: Chuck R Greenfeld, Katherine F Roby, Melissa E Pepling, Janice K Babus, Paul F Terranova, Jodi A FlawsAbstract:Abstract It is believed that a finite pool of primordial follicles is established during embryonic and neonatal life. At birth, the mouse ovary consists of clusters of interconnected oocytes surrounded by pregranulosa cells. Shortly after birth these structures, termed germ cell cysts or nests (GCN), break down to facilitate primordial follicle formation. Tumor necrosis factor alpha (TNF) is a widely expressed protein with myriad functions. TNF is expressed in the ovary and may regulate GCN breakdown in rats. We investigated whether it participates in GCN breakdown and follicle formation in mice by using an in vitro ovary culture system as well as mutant animal models. We found that TNF and both receptors (TNFRSF1A and TNFRSF1B) are expressed in neonatal mouse ovaries and that TNF promotes oocyte death in neonatal ovaries in vitro. However, deletion of either receptor did not affect follicle endowment, suggesting that TNF does not regulate GCN breakdown in vivo. Tnfrsf1b deletion led to an apparent accele...
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tumor necrosis factor tnf receptor type 2 is an important mediator of tnf alpha function in the mouse ovary
Biology of Reproduction, 2007Co-Authors: Chuck R Greenfeld, Katherine F Roby, Melissa E Pepling, Janice K Babus, Paul F Terranova, Jodi A FlawsAbstract:It is believed that a finite pool of primordial follicles is established during embryonic and neonatal life. At birth, the mouse ovary consists of clusters of interconnected oocytes surrounded by pregranulosa cells. Shortly after birth these structures, termed germ cell cysts or nests (GCN), break down to facilitate primordial follicle formation. Tumor necrosis factor alpha (TNF) is a widely expressed protein with myriad functions. TNF is expressed in the ovary and may regulate GCN breakdown in rats. We investigated whether it participates in GCN breakdown and follicle formation in mice by using an in vitro ovary culture system as well as mutant animal models. We found that TNF and both receptors (TNFRSF1A and TNFRSF1B) are expressed in neonatal mouse ovaries and that TNF promotes oocyte death in neonatal ovaries in vitro. However, deletion of either receptor did not affect follicle endowment, suggesting that TNF does not regulate GCN breakdown in vivo. Tnfrsf1b deletion led to an apparent acceleration of follicular growth and a concomitant expansion of the primordial follicle population. This expansion of the primordial follicle population does not appear to be due to decreased primordial follicle atresia, although this cannot be ruled out completely. This study demonstrates that mouse oocytes express both TNF receptors and are sensitive to TNF-induced death. Additionally, TNFRSF1B is demonstrated to be an important mediator of TNF function in the mouse ovary and an important regulator of folliculogenesis.
Ulrich Salzer - One of the best experts on this subject based on the ideXlab platform.
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heterozygous alterations of TNFRSF13B taci in tonsillar hypertrophy and sarcoidosis
Clinical & Developmental Immunology, 2013Co-Authors: Matthaios Speletas, Ulrich Salzer, Zoe Florou, Efthimia Petinaki, Zoe Daniil, Fotini Bardaka, Konstantinos I Gourgoulianis, Charalampos Skoulakis, Anastasios E GermenisAbstract:TNFRSF13B/TACI defects have been associated with CVID pathogenesis and/or phenotype, especially the development of benign lymphoproliferation and autoimmunity. Our purpose was to investigate the role of TNFRSF13B/TACI defects in the pathogenesis of two common lymphoproliferative disorders, namely, sarcoidosis and tonsillar hypertrophy (TH). 105 patients (71 with sarcoidosis and 34 with TH, including 19 without infectious causative and 15 due to Haemophilus influenzae) were analyzed for TNFRSF13B/TACI defects. Two out of 19 TH patients without infectious cause (10.5%) and 2 patients with sarcoidosis (2.8%) displayed rare TNFRSF13B/TACI defects (I87N, L69TfsX12, E36L, and R202H, resp.). Both mutations identified in TH patients have been assessed as deleterious for protein function, while the patient with the R202H mutation and sarcoidosis exhibited also sIgG4D. Our study further supports the notion that TNFRSF13B/TACI defects alone do not result in CVID but may be also found frequently in distinct clinical phenotypes, including benign lymphoproliferation and IgG subclass deficiencies.
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sequence variants of the TNFRSF13B gene in czech cvid and igad patients in the context of other populations
Human Immunology, 2012Co-Authors: Tomas Freiberger, Ulrich Salzer, Barbora Ravcukova, Lucie Grodecka, Z Pikulova, Dagmar Stikarovska, Sava Pesak, Pavel Kuklinek, Jiři Jarkovský, Jiři LitzmanAbstract:Mutations in the TNFRSF13B gene, encoding TACI, have been found in common variable immunodefi- ciency (CVID) and selective IgA deficient (IgAD) patients, but only the association with CVID seems to be significant. In this study, Czech CVID, IgAD and primary hypo/dysgammaglobulinemic (HG/DG) patients were screened for all TNFRSF13B sequence variants. The TNFRSF13B gene was mutated in 4/70 CVID patients (5.7%), 9/161 IgAD patients (5.6%), 1/17 HG/DG patient (5.9%) and none of 195 controls. Eight different mutations were detected, including the most frequent p.C104R and p.A181E mutations as well as 1 novel missense mutation, p.R189K. A significant association of TNFRSF13B gene mutations was observed in both CVID (p = 0.01) and IgAD (p = 0.002) Czech patients. However, when combined with all published data, only the association with CVID remained significant compared with the controls (9.9% vs. 3.2%, p < 10^6), while statistical significance disappeared for IgAD (5.7% vs. 3.2%, p = 0.145). The silent mutation p.P97P was shown to be associated significantly with CVID compared with the controls in both Czech patients (allele frequency 4.3% vs. 0.2%, p = 0.01) and in connection with the published data (5.1% vs. 1.8%, p = 0.003). The relevance of some TNFRSF13B gene variants remains unclear and needs to be elu- cidated in future studies.
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novel mutations in taci TNFRSF13B causing common variable immunodeficiency
Journal of Clinical Immunology, 2009Co-Authors: Javad Mohammadi, Ulrich Salzer, Qiang Panhammarstrom, Astrid Bergbreiter, Chonghai Liu, Asghar Aghamohammadi, Nima Rezaei, Ali Akbar Amirzargar, Mostafa Moin, Lennart HammarstromAbstract:Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production. The disorder is also characterized by co-occurrence of autoimmune, lymphoproliferative, and granulomatous diseases. Mutations in the gene encoding TACI (Transmembrane Activator and CAML Interactor, TNFRSF13B) were previously found to be associated with CVID. We therefore sequenced TNFRSF13B gene in a cohort of 48 Iranian CVID patients. Expression of TACI and binding of A proliferation-inducing ligand (APRIL) were tested by FACS. We identified one patient with a homozygous G to T substitution in the TNFRSF13B gene at the splice site of intron 1 (c.61+1G>T), which abolished expression of the TACI molecule and binding capacity of APRIL. This represents the second CVID patient in the world with a complete absence of TACI expression. B cell lines from family members carrying the same mutation in a heterozygous form showed a reduced level of TACI expression and APRIL-binding capacity, suggesting a gene dosage effect. In addition, we found the previously recognized C104R and C172Y mutations in a heterozygous form in two patients with CVID and one, novel, heterozygous P42T mutation. TACI mutations were observed in Iran CVID patients in a similar frequency as in other Caucasian populations. The novel mutations identified in this study support the notion of a crucial role for TACI in B cell differentiation.
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relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease causing from risk increasing TNFRSF13B variants in antibody deficiency syndromes
Blood, 2009Co-Authors: Ulrich Salzer, Chiara Bacchelli, Sylvie Buckridge, Qiang Panhammarstrom, Stephanie Jennings, Vassilis Lougaris, Astrid Bergbreiter, Tina Hagena, Jennifer Birmelin, Alessandro PlebaniAbstract:TNFRSF13B encodes transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a B cell– specific tumor necrosis factor (TNF) receptor superfamily member. Both biallelic and monoallelic TNFRSF13B mutations were identified in patients with common variable immunodeficiency disorders. The genetic complexity and variable clinical presentation of TACI deficiency prompted us to evaluate the genetic, immunologic, and clinical condition in 50 individuals with TNFRSF13B alterations, following screening of 564 unrelated patients with hypogammaglobulinemia. We identified 13 new sequence variants. The most frequent TNFRSF13B variants (C104R and A181E; n = 39; 6.9%) were also present in a heterozygous state in 2% of 675 controls. All patients with biallelic mutations had hypogammaglobulinemia and nearly all showed impaired binding to a proliferation-inducing ligand (APRIL). However, the majority (n = 41; 82%) of the pa-tients carried monoallelic changes in TNFRSF13B. Presence of a heterozygous mutation was associated with antibody deficiency (P <.001, relative risk 3.6). Heterozygosity for the most common mutation, C104R, was associated with disease (P < .001, relative risk 4.2). Furthermore, heterozygosity for C104R was associated with low numbers of IgD−CD27+ B cells (P = .019), benign lymphoproliferation (P < .001), and autoimmune complications (P = .001). These associations indicate that C104R heterozygosity increases the risk for common variable immunodeficiency disorders and influences clinical presentation.
Necil Kutukculer - One of the best experts on this subject based on the ideXlab platform.
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TNFRSF13B taci alterations in turkish patients with common variable immunodeficiency and iga deficiency
Avicenna journal of medical biotechnology, 2018Co-Authors: Neslihan Edeer Karaca, Guzide Aksu, Ezgi Ulusoy Severcan, Burcu Guven, Elif Azarsiz, Necil KutukculerAbstract:Background The Transmembrane Activator and Calcium modulator ligand Interactor (TACI), encoded by TNFRSF13B/TACI gene, is mutated in some patients with Common Variable Immunodeficiency (CVID) and IgA Deficiency (IgAD). The purpose of the study was to investigate for the first time in Turkish patients the prevalence of TNFRSF13B alterations in CVID, selective and partial IgAD patients. Methods Forty two CVID, 36 selective IgAD, 34 partial IgAD and 25 healthy controls were included. All patients were examined for TNFRSF13B gene mutations by PCR. Results The percentages of TNFRSF13B mutations in CVID, selective and partial IgAD patients were 7.1, 2.7 and 2.9%, respectively. No disease causing TNFRSF13B mutation in healthy controls was found. Patients with TACI mutations had recurrent respiratory tract infections. None of them experienced autoimmunity, bronchiectasis or granulomatous disease. In conclusion, TNFRSF13B mutations were present not only in CVID patients, but also in IgAD cases. Conclusion Modifier genes as well as their combination with other genetic or environmental factors may play an important role in the development of the immunodeficiency phenotype.
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Three Different Classifications, B Lymphocyte Subpopulations, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) Gene Mutations, CTLA-4 and ICOS Gene Polymorphisms in Turkish Patients with Common Variable Immunodeficiency
Journal of clinical immunology, 2012Co-Authors: Necil Kutukculer, Nesrin Gulez, Neslihan Edeer Karaca, Guzide Aksu, Afig BerdeliAbstract:B lymphocyte subpopulations, previously defined classification schemes (Freiburg, Paris, EuroClass), TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) gene mutations, CTLA-4 and ICOS gene polymorphisms were analyzed in 25 common variable immunodeficiency (CVID) patients and 25 healthy controls. Patients were also divided into two subgroups due to some disease severity criteria. SG (severe disease group) (n:11) included patients who have splenomegaly and/or granulomatous diseases and/or bronchiectasis and/or lower baseline IgG values ( G changes in exon 1 of CTLA-4 gene: GG and AG genotypes increase the risk of CVID development 1.32 and 2.18 fold, respectively. 1564 T > C polymorphisms on 3′UTR region in exon 2 of ICOS gene was not found to be significantly different in CVID patients. CVID classifications were not helpful in determining the genetic etiology of CVID.
Lennart Hammarstrom - One of the best experts on this subject based on the ideXlab platform.
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rare mutations in TNFRSF13B increase the risk of asthma symptoms in swedish children
Genes and Immunity, 2012Co-Authors: Magdalena Janzi, Erik Melen, Inger Kull, Magnus Wickman, Lennart HammarstromAbstract:TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) mutations seem to be associated with autoimmunity and common variable immunodeficiency in humans. Because of its role in immune responses, we investigated the association between TACI mutations and infection proneness/asthma symptoms in children. A total of 2372 children were genotyped for TACI mutations (I87N, C104R, S144X, A181E, R202H and ins204A). Serum IgA, IgG and specific IgE levels were determined in children with mutations. Data on parentally reported allergic diseases and infections were collected. In all, 55 individuals with TACI mutations were identified. Children with TACI mutations had a 2-fold increased risk of wheeze at 2 and 4 years of age and a 2.5-fold increased risk of asthma was seen at 4 years of age. None of the children with mutations suffered from IgA deficiency (<0.07 g l−1). No significant differences in serum IgG levels or specific IgE were found. Common variants in asthma susceptibility genes may account for up to 40% of cases of childhood-onset asthma, indicating a high contribution, compared with other common disorders. The role of rare variants/mutations in the pathogenesis of asthma is less clear. We conclude that mutations in TACI are the contributing factors for asthma symptoms in Swedish children, although the mechanisms still remain elusive.
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novel mutations in taci TNFRSF13B causing common variable immunodeficiency
Journal of Clinical Immunology, 2009Co-Authors: Javad Mohammadi, Ulrich Salzer, Qiang Panhammarstrom, Astrid Bergbreiter, Chonghai Liu, Asghar Aghamohammadi, Nima Rezaei, Ali Akbar Amirzargar, Mostafa Moin, Lennart HammarstromAbstract:Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production. The disorder is also characterized by co-occurrence of autoimmune, lymphoproliferative, and granulomatous diseases. Mutations in the gene encoding TACI (Transmembrane Activator and CAML Interactor, TNFRSF13B) were previously found to be associated with CVID. We therefore sequenced TNFRSF13B gene in a cohort of 48 Iranian CVID patients. Expression of TACI and binding of A proliferation-inducing ligand (APRIL) were tested by FACS. We identified one patient with a homozygous G to T substitution in the TNFRSF13B gene at the splice site of intron 1 (c.61+1G>T), which abolished expression of the TACI molecule and binding capacity of APRIL. This represents the second CVID patient in the world with a complete absence of TACI expression. B cell lines from family members carrying the same mutation in a heterozygous form showed a reduced level of TACI expression and APRIL-binding capacity, suggesting a gene dosage effect. In addition, we found the previously recognized C104R and C172Y mutations in a heterozygous form in two patients with CVID and one, novel, heterozygous P42T mutation. TACI mutations were observed in Iran CVID patients in a similar frequency as in other Caucasian populations. The novel mutations identified in this study support the notion of a crucial role for TACI in B cell differentiation.
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variants in antibody deficiency syndromes TNFRSF13B distinguishing disease causing from risk increasing mutations in TNFRSF13B relevance of biallelic versus monoallelic
2009Co-Authors: B Gaspar, Lennart Hammarstrom, B Grimbacher, Michael E Gertz, Alejandro A Schaffer, Dinakantha S Kumararatne, Tatiana C Lawrence, Jose Luis Franco, Stephanie Anoversombke, Hans D OchsAbstract:doi:10.1182/blood-2008-02-141937 Prepublished online Nov 3, 2008;2009 113: 1967-1976€€€€Thrasher, H. Bobby Gaspar and Bodo Grimbacher Schulze, Pascal Schneider, E. Michael Gertz, Alejandro A. Schaffer, Lennart Hammarstrom, Adrian J.Ugrinovic, Dinakantha S. Kumararatne, Tatiana C. Lawrence, Are M. Holm, Jose L. Franco, Ilka Spickett, Stephanie Anover-Sombke, Hans D. Ochs, Simon Urschel, Bernd H. Belohradsky, SanjaWebster, Hans-Hartmut Peter, Daniel Suez, Helen Chapel, Andrew McLean-Tooke, Gavin P. Vassilis Lougaris, Astrid Bergbreiter, Tina Hagena, Jennifer Birmelin, Alessandro Plebani, A. David B.Ulrich Salzer, Chiara Bacchelli, Sylvie Buckridge, Qiang Pan-Hammarstrom, Stephanie Jennings,€
Anastasios E Germenis - One of the best experts on this subject based on the ideXlab platform.
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heterozygous alterations of TNFRSF13B taci in tonsillar hypertrophy and sarcoidosis
Clinical & Developmental Immunology, 2013Co-Authors: Matthaios Speletas, Ulrich Salzer, Zoe Florou, Efthimia Petinaki, Zoe Daniil, Fotini Bardaka, Konstantinos I Gourgoulianis, Charalampos Skoulakis, Anastasios E GermenisAbstract:TNFRSF13B/TACI defects have been associated with CVID pathogenesis and/or phenotype, especially the development of benign lymphoproliferation and autoimmunity. Our purpose was to investigate the role of TNFRSF13B/TACI defects in the pathogenesis of two common lymphoproliferative disorders, namely, sarcoidosis and tonsillar hypertrophy (TH). 105 patients (71 with sarcoidosis and 34 with TH, including 19 without infectious causative and 15 due to Haemophilus influenzae) were analyzed for TNFRSF13B/TACI defects. Two out of 19 TH patients without infectious cause (10.5%) and 2 patients with sarcoidosis (2.8%) displayed rare TNFRSF13B/TACI defects (I87N, L69TfsX12, E36L, and R202H, resp.). Both mutations identified in TH patients have been assessed as deleterious for protein function, while the patient with the R202H mutation and sarcoidosis exhibited also sIgG4D. Our study further supports the notion that TNFRSF13B/TACI defects alone do not result in CVID but may be also found frequently in distinct clinical phenotypes, including benign lymphoproliferation and IgG subclass deficiencies.
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TNFRSF13B taci alterations in greek patients with antibody deficiencies
Journal of Clinical Immunology, 2011Co-Authors: Matthaios Speletas, Fotini Bardaka, Antigoni Mamara, Efimia Papadopouloualataki, George Iordanakis, Kyriaki Liadaki, Maria Kanariou, Anastasios E GermenisAbstract:TNFRSF13B/TACI defects have recently been associated with common variable immunodeficiency (CVID) pathogenesis. Considering that TNFRSF13B/TACI is very polymorphic and the frequency of its alterations may be different in various ethnic groups, we analyzed their prevalence in 47 Greek patients with antibody deficiencies, including CVID (16 patients), IgAD (16 patients), selective IgG4D (11 patients), and transient hypogammaglobulinemia of infancy (4 patients). A rather high frequency of TNFRSF13B/TACI defects was identified in patients with selective IgG4D (18.18%). Moreover, a patient with CVID was heterozygous in the common C104R mutation (6.25%). Both his children and a further healthy individual carried the same mutation, albeit without recurrent infections and/or hypogammaglobulinemia. The common polymorphisms V220A and P251L were identified in all disease subgroups, in an almost similar frequency with that observed in 259 healthy controls. Our data provide further evidence that TNFRSF13B/TACI alterations are not causative of CVID. Possibly, they predispose to humoral deficiencies and/or contribute to their phenotype when combined with other immune gene alterations.
