The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform

Sebastiaan Engelborghs - One of the best experts on this subject based on the ideXlab platform.

  • alzheimer risk associated with a copy number variation in the Complement Receptor 1 increasing c3b c4b binding sites
    Molecular Psychiatry, 2012
    Co-Authors: Nathalie Brouwers, Karolien Bettens, Sebastiaan Engelborghs, C Van Cauwenberghe, Jc Lambert, Le N Bastard, Florence Pasquier, Gil A Montoya
    Abstract:

    Two multicentre genome-wide association (GWA) studies provided substantial evidence, implicating the Complement Receptor 1 gene (CR1) in Alzheimer disease (AD) genetic etiology. CR1 encodes a large transmembrane Receptor with a crucial role in the immune Complement cascade. We performed a genetic follow-up of the GWA CR1 association in a Flanders–Belgian cohort (n=1883), and investigated the effect of single-nucleotide polymorphisms (SNPs) located in the CR1 locus on AD risk and cerebrospinal fluid (CSF) biomarker levels. We obtained significant association (Padj<0.03; odds ratio (OR)=1.24 (95% confidence interval (CI): 1.02–1.51)) for one CR1 risk haplotype, and haplotype association was strongest in individuals carrying apolipoprotein E (APOE) ɛ4 alleles (Padj<0.006; OR=1.50 (95% CI: 1.08–2.09)). Also, four SNPs correlated with increased CSF amyloid Aβ1−42 levels, suggesting a role for the CR1 protein in Aβ metabolism. Moreover, we quantified a low-copy repeat (LCR)-associated copy number variation (CNV) in CR1, producing different CR1 isoforms, CR1-F and CR1-S, and obtained significant association in carriers of CR1-S. We replicated the CR1 CNV association finding in a French cohort (n=2003) and calculated in the combined cohorts, an OR of 1.32; 95% CI: 1.10–1.59 (P=0.0025). Our data showed that the common AD risk association may well be explained by the presence of CR1-S increasing the number of C3b/C4b and cofactor activity sites and AD risk with 30% in CR1-S carriers. How precisely the different functional role of CR1-S in the immune Complement cascade contributes to AD pathogenesis will need additional functional studies.

  • Alzheimer risk associated with a copy number polymorphism in the Complement Receptor 1 increasing C3b/C4b binding sites
    Molecular Psychiatry, 2011
    Co-Authors: Christine Van Broeckhoven, Nathalie Brouwers, Caroline Van Cauwenberghe, Karolien Bettens, Ana Gil Montoya, Karin Peeters, Maria Mattheijssens, Marc Cruts, Kristel Sleegers, Sebastiaan Engelborghs
    Abstract:

    Two multicentre genome-wide association (GWA) studies provided substantial evidence implicating the Complement Receptor 1 gene (CR1) in Alzheimer disease (AD) genetic etiology. CR1 encodes a large transmembrane Receptor with a crucial role in the immune Complement cascade. We performed a genetic follow-up of the GWA CR1 association in a Flanders-Belgian cohort (n= 1883), and investigated the effect of single nucleotide polymorphisms (SNPs) located in the CR1 locus on AD risk and cerebrospinal fluid (CSF) biomarker levels. We obtained significant association (padj

George C. Tsokos - One of the best experts on this subject based on the ideXlab platform.

  • Regulation of Complement Receptor Gene Expression
    The Complement System, 2020
    Co-Authors: Mate Tolnay, George C. Tsokos
    Abstract:

    Complement Receptors form a critical interface between extracellular Complement activation and intracellular signaling. The proper cellular response to Complement fragments depends on cell-specific expression of Complement Receptors at precise cell surface densities. An array of transcription factors binding to promoter elements of the Complement Receptor genes regulate Complement Receptor mRNA and, ultimately, protein levels. In addition, specific extracellular stimuli modify Complement Receptor expression levels that, in turn, alter the capacity of the cell to respond to Complement fragments.

  • Complement Receptor 1 is a sialic acid independent erythrocyte Receptor of plasmodium falciparum
    PLOS Pathogens, 2010
    Co-Authors: George C. Tsokos, Carmenza Spadafora, Gordon A Awandare, Karen M Kopydlowski, Jozsef Czege, Kathleen J Moch, Robert W Finberg
    Abstract:

    Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood. P. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. However, a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. The identity of the erythrocyte sialic acid-independent Receptor has been a mystery for decades. We report here that the Complement Receptor 1 (CR1) is a sialic acid-independent Receptor for the invasion of erythrocytes by P. falciparum. We show that soluble CR1 (sCR1) as well as polyclonal and monoclonal antibodies against CR1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates, and that merozoites interact directly with CR1 on the erythrocyte surface and with sCR1coated microspheres. Also, the invasion of neuraminidase-treated erythrocytes correlates with the level of CR1 expression. Finally, both sialic acid-independent and dependent strains invade CR1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. These results suggest that both sialic acid-dependent and independent strains interact with CR1 in the normal red cell during the invasion process. However, only sialic acid-independent strains can do so without the presence of glycophorin sialic acid. Our results close a longstanding and important gap in the understanding of the mechanism of erythrocyte invasion by P. falciparum that will eventually make possible the development of an effective blood stage vaccine.

  • anti phospholipid antibodies restore mesenteric ischemia reperfusion induced injury in Complement Receptor 2 Complement Receptor 1 deficient mice
    Journal of Immunology, 2004
    Co-Authors: Michael V Holers, Sherry D Fleming, Ryan Egan, Chunyan Chai, Guillermina Girardi, Jane E Salmon, Marc Monestier, George C. Tsokos
    Abstract:

    Complement Receptor 2-deficient ( Cr2 −/− ) mice are resistant to mesenteric ischemia/reperfusion (I/R) injury because they lack a component of the natural Ab repertoire. Neither the nature of the Abs that are involved in I/R injury nor the composition of the target Ag, to which recognition is lacking in Cr2 −/− mice, is known. Because anti-phospholipid Abs have been shown to mediate fetal growth retardation and loss when injected into pregnant mice, we performed experiments to determine whether anti-phospholipid Abs can also reconstitute I/R injury and, therefore, represent members of the injury-inducing repertoire that is missing in Cr2 −/− mice. We demonstrate that both murine and human monoclonal and polyclonal Abs against negatively charged phospholipids can reconstitute mesenteric I/R-induced intestinal and lung tissue damage in Cr2 −/− mice. In addition, Abs against β2 glycoprotein I restore local and remote tissue damage in the Cr2 −/− mice. Unlike Cr2 −/− mice, reconstitution of I/R tissue damage in the injury-resistant Rag-1 −/− mouse required the infusion of both anti-β2-glycoprotein I and anti-phospholipid Ab. We conclude that anti-phospholipid Abs can bind to tissues subjected to I/R insult and mediate tissue damage.

  • Complement Receptor 2 in the Regulation of the Immune Response
    Clinical Immunology and Immunopathology, 1998
    Co-Authors: Mate Tolnay, George C. Tsokos
    Abstract:

    Antigens coated with split products of C3, the result of Complement activation, are capable of crosslinking the Complement Receptor 2 (CR2, CD21) and the antigen Receptor on the surface of B cells simultaneously. This dual recognition leads to increased cell proliferation and differentiation and enhanced antibody production. CR2 is also considered to be a regulator of the B cell response to antigen. In this review we summarize the biology of the CR2 and focus on its essential role in generating an effective B cell response to antigenic stimuli. The involvement of CR2 in the pathophysiology of infectious and autoimmune diseases is also discussed.

Jc Lambert - One of the best experts on this subject based on the ideXlab platform.

  • alzheimer risk associated with a copy number variation in the Complement Receptor 1 increasing c3b c4b binding sites
    Molecular Psychiatry, 2012
    Co-Authors: Nathalie Brouwers, Karolien Bettens, Sebastiaan Engelborghs, C Van Cauwenberghe, Jc Lambert, Le N Bastard, Florence Pasquier, Gil A Montoya
    Abstract:

    Two multicentre genome-wide association (GWA) studies provided substantial evidence, implicating the Complement Receptor 1 gene (CR1) in Alzheimer disease (AD) genetic etiology. CR1 encodes a large transmembrane Receptor with a crucial role in the immune Complement cascade. We performed a genetic follow-up of the GWA CR1 association in a Flanders–Belgian cohort (n=1883), and investigated the effect of single-nucleotide polymorphisms (SNPs) located in the CR1 locus on AD risk and cerebrospinal fluid (CSF) biomarker levels. We obtained significant association (Padj<0.03; odds ratio (OR)=1.24 (95% confidence interval (CI): 1.02–1.51)) for one CR1 risk haplotype, and haplotype association was strongest in individuals carrying apolipoprotein E (APOE) ɛ4 alleles (Padj<0.006; OR=1.50 (95% CI: 1.08–2.09)). Also, four SNPs correlated with increased CSF amyloid Aβ1−42 levels, suggesting a role for the CR1 protein in Aβ metabolism. Moreover, we quantified a low-copy repeat (LCR)-associated copy number variation (CNV) in CR1, producing different CR1 isoforms, CR1-F and CR1-S, and obtained significant association in carriers of CR1-S. We replicated the CR1 CNV association finding in a French cohort (n=2003) and calculated in the combined cohorts, an OR of 1.32; 95% CI: 1.10–1.59 (P=0.0025). Our data showed that the common AD risk association may well be explained by the presence of CR1-S increasing the number of C3b/C4b and cofactor activity sites and AD risk with 30% in CR1-S carriers. How precisely the different functional role of CR1-S in the immune Complement cascade contributes to AD pathogenesis will need additional functional studies.

Nathalie Brouwers - One of the best experts on this subject based on the ideXlab platform.

  • alzheimer risk associated with a copy number variation in the Complement Receptor 1 increasing c3b c4b binding sites
    Molecular Psychiatry, 2012
    Co-Authors: Nathalie Brouwers, Karolien Bettens, Sebastiaan Engelborghs, C Van Cauwenberghe, Jc Lambert, Le N Bastard, Florence Pasquier, Gil A Montoya
    Abstract:

    Two multicentre genome-wide association (GWA) studies provided substantial evidence, implicating the Complement Receptor 1 gene (CR1) in Alzheimer disease (AD) genetic etiology. CR1 encodes a large transmembrane Receptor with a crucial role in the immune Complement cascade. We performed a genetic follow-up of the GWA CR1 association in a Flanders–Belgian cohort (n=1883), and investigated the effect of single-nucleotide polymorphisms (SNPs) located in the CR1 locus on AD risk and cerebrospinal fluid (CSF) biomarker levels. We obtained significant association (Padj<0.03; odds ratio (OR)=1.24 (95% confidence interval (CI): 1.02–1.51)) for one CR1 risk haplotype, and haplotype association was strongest in individuals carrying apolipoprotein E (APOE) ɛ4 alleles (Padj<0.006; OR=1.50 (95% CI: 1.08–2.09)). Also, four SNPs correlated with increased CSF amyloid Aβ1−42 levels, suggesting a role for the CR1 protein in Aβ metabolism. Moreover, we quantified a low-copy repeat (LCR)-associated copy number variation (CNV) in CR1, producing different CR1 isoforms, CR1-F and CR1-S, and obtained significant association in carriers of CR1-S. We replicated the CR1 CNV association finding in a French cohort (n=2003) and calculated in the combined cohorts, an OR of 1.32; 95% CI: 1.10–1.59 (P=0.0025). Our data showed that the common AD risk association may well be explained by the presence of CR1-S increasing the number of C3b/C4b and cofactor activity sites and AD risk with 30% in CR1-S carriers. How precisely the different functional role of CR1-S in the immune Complement cascade contributes to AD pathogenesis will need additional functional studies.

  • Alzheimer risk associated with a copy number polymorphism in the Complement Receptor 1 increasing C3b/C4b binding sites
    Molecular Psychiatry, 2011
    Co-Authors: Christine Van Broeckhoven, Nathalie Brouwers, Caroline Van Cauwenberghe, Karolien Bettens, Ana Gil Montoya, Karin Peeters, Maria Mattheijssens, Marc Cruts, Kristel Sleegers, Sebastiaan Engelborghs
    Abstract:

    Two multicentre genome-wide association (GWA) studies provided substantial evidence implicating the Complement Receptor 1 gene (CR1) in Alzheimer disease (AD) genetic etiology. CR1 encodes a large transmembrane Receptor with a crucial role in the immune Complement cascade. We performed a genetic follow-up of the GWA CR1 association in a Flanders-Belgian cohort (n= 1883), and investigated the effect of single nucleotide polymorphisms (SNPs) located in the CR1 locus on AD risk and cerebrospinal fluid (CSF) biomarker levels. We obtained significant association (padj

John B. Harley - One of the best experts on this subject based on the ideXlab platform.

  • Complement Receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing
    Genes and Immunity, 2009
    Co-Authors: Katherine B. Douglas, Daniel C. Windels, Jian Zhao, Agnessa V. Gadeliya, Hui Wu, Kenneth M. Kaufman, John B. Harley, Joan T. Merrill, Robert P. Kimberly, Graciela S. Alarcón
    Abstract:

    Complement Receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing

  • polymorphisms of Complement Receptor 1 and interleukin 10 genes and systemic lupus erythematosus a meta analysis
    Human Genetics, 2005
    Co-Authors: John B. Harley, Swapan K Nath
    Abstract:

    A number of studies have tested the association of the Complement Receptor 1 (CR1) and Interleukin-10 (IL10) polymorphisms with systemic lupus erythematosus (SLE), but reported conflicting results. The aim of the study is to explore whether the CR1 and IL10 genes are associated with SLE susceptibility. We surveyed studies on the CR1 and IL10 polymorphisms and SLE using comprehensive Medline search and review of the references. A meta-analysis was conducted in a fixed effects model or random effects model based on between-study heterogeneity. Eighteen comparisons from 13 studies were included in the CR1 meta-analysis and a total of 16 separate comparisons were used for the IL10 meta-analysis. The CR1 meta-analysis showed no significant association of the CR1 functional polymorphisms with SLE. In contrast, the S structural variant of the CR1 showed a significant association (OR=1.544, 95% CI, 1.217–1.959, P<0.001). Stratification by ethnicity indicated that the CR1 S variant was associated with SLE in Caucasians (OR=1.667, 95% CI, 1.193–2.357, P=0.003). The IL10 meta-analysis showed a significant association between SLE and the G11 allele of IL10.G (OR=1.279, 95% CI; 1.027–1.593, P=0.028) in whole populations, and IL10 promoter −1082G allele was associated with SLE in Asians (OR=1.358, 95% CI; 1.015–1.816, P=0.039). In conclusion, the CR1 meta-analysis revealed the association of the S structural variant of the CR1 with SLE and the IL10 meta-analysis showed the association of IL10.G11 allele and SLE in whole populations and the association between promoter -A1082G polymorphism and SLE in Asians.