{Reference Type}: Journal Article
{Author}: Dieude, P.; Guedj, M.; Wipff, J.; Ruiz, B.; Riemekasten, G.; Airo, P.; Melchers, I.; Hachulla, E.; Cerinic, M. Matucci; Diot, E.; Hunzelmann, N.; Caramaschi, P.; Sibilia, J.; Tiev, K.; Mouthon, L.; Riccieri, V.; Cracowski, J. L.; Carpentier, P. H.; Distler, J.; Amoura, Z.; Tarner, I.; Avouac, J.; Meyer, O.; Kahan, A.; Boileau, C.; Allanore, Y.
{Year}: 2011
{Title}: NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis
{Tag}: 0
{Star}: 0
{Journal}: ANNALS OF THE RHEUMATIC DISEASES
{Volume}: 70
{Issue}: 4
{Pages}: 668-674
{ISBN/ISSN}: 0003-4967
{Keywords}: AUTOIMMUNE ADDISONS-DISEASE; GENETIC RISK-FACTOR; PULMONARY-FIBROSIS; AUTOINFLAMMATORY DISEASES; FUNCTIONAL POLYMORPHISM; INFLAMMATORY CASPASES; SCLERODERMA; INTERLEUKIN-1-BETA; FIBROBLASTS; NALP1
{Abstract}: Background Recent evidence has highlighted a potential role of interleukin 1 beta (IL-1 beta) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1 beta. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders.
Objective To study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population.
Methods NLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin.
Results Conditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA.
Conclusions Our results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.
{Author Address}: Paris Diderot Univ, Dept Rheumatol, Serv Rhumatol, Hop Bichat Claude Bernard,AP HP,INSERM U699, F-75018 Paris, France; Univ Evry Val dEssonne, Lab Stat & Genome, UMR CNRS 8071, INRA 1152, Evry, France; Paris Diderot Univ, Necker Hosp, INSERM U781, F-75018 Paris, France; Paris Descartes Univ, Cochin Hosp, INSERM U1016, Dept Rheumatol A, Paris, France; Paris Diderot Univ, Necker Hosp, INSERM U781, F-75018 Paris, France; Charite, Dept Rheumatol & Clin Immunol, Berlin, Germany; Spedali Civil Brescia, I-25125 Brescia, Italy; Univ Med Ctr, Clin Res Unit Rheumatol, Freiburg, Germany; Univ Lille 2, Dept Internal Med, Lille, France; Dept Biomed, Rheumatol Sect, Florence, Italy; CHU Bretonneau, IFR 135, INSERM U618, F-37044 Tours, France; Univ Cologne, Dept Dermatol, D-5000 Cologne, Germany; Univ Verona, Rheumatol Unit, Dept Clin & Expt Med, I-37100 Verona, Italy; Univ Strasbourg 1, Serv Rhumatol, Hop Hautepierre, Strasbourg, France; Univ Paris 06, St Antoine Hosp, APHP, Paris, France; Paris Descartes Univ, Dept Internal Med, Cochin Hosp, APHP, Paris, France; Univ Roma La Sapienza, Dept Med Clin & Therapy, Div Rheumatol, Rome, Italy; CHU Grenoble, INSERM CIC3, F-38043 Grenoble, France; CHU Grenoble, Clin Univ Med Vasc, F-38043 Grenoble, France; Univ Erlangen Nurnberg, Dept Internal Med 3, Erlangen, Germany; Univ Erlangen Nurnberg, Inst Clin Immunol, Erlangen, Germany; Univ Paris 06, Dept Internal Med 2, Pitie Salpetriere Hosp, APHP, Paris, France; Univ Giessen, Dept Rheumatol & Clin Immunol, Kerckhoff Clin, Bad Nauheim, Germany; Paris Diderot Univ, Necker Hosp, INSERM U781, F-75018 Paris, France; Paris Descartes Univ, Cochin Hosp, INSERM U1016, Dept Rheumatol A, Paris, France;
<AuCollectiveName>Meyer, O.</AuCollectiveName>
</fullauthorname>
<author>Kahan, A</author>
<fullauthorname>
<AuRole>Author</AuRole>
<AuLastName>Kahan</AuLastName>
<AuFirstName>A.</AuFirstName>
<address number="4">Paris Descartes Univ, Cochin Hosp, INSERM U1016, Dept Rheumatol A, Paris, France; Paris Diderot Univ, Necker Hosp, INSERM U781, F-75018 Paris, France; St Quentin Yvelines Univ, Lab Biochim Hormonale &amp; Genet, Ambroise Pare Hosp, APHP, Boulogne, France; Paris Diderot Univ, Necker Hosp, INSERM U781, F-75018 Paris, France; Paris Descartes Univ, Cochin Hosp, INSERM U1016, Dept Rheumatol A, Paris, France
{Database Provider}: Web of Science SCI
{Language}: English
{Country}: France; France; France; France; Germany; Italy; Germany; France; Italy; France; Germany; Italy; France; France; France; Italy; France; France; Germany; Germany; France; Germany; France

{Reference Type}: Journal Article
{Author}: Eloranta, Maija-Leena; Franck-Larsson, Karin; Lovgren, Tanja; Kalamajski, Sebastian; Ronnblom, Anders; Rubin, Kristofer; Alm, Gunnar V.; Ronnblom, Lars
{Year}: 2010
{Title}: Type I interferon system activation and association with disease manifestations in systemic sclerosis
{Tag}: 0
{Star}: 0
{Journal}: ANNALS OF THE RHEUMATIC DISEASES
{Volume}: 69
{Issue}: 7
{Pages}: 1396-1402
{ISBN/ISSN}: 0003-4967
{Keywords}: PRIMARY SJOGRENS-SYNDROME; PLASMACYTOID DENDRITIC CELLS; PERIPHERAL-BLOOD CELLS; LUPUS-ERYTHEMATOSUS; GENE-EXPRESSION; IMMUNE-COMPLEXES; ALPHA; SCLERODERMA; RNA; AUTOANTIBODIES
{Abstract}: Objectives To study the presence of interferogenic autoantibodies in systemic sclerosis (SSc) and their correlation with clinical manifestations, serum levels of interferon alpha (IFN alpha) and chemokines of importance in the disease process.
Methods Peripheral blood mononuclear cells (PBMCs) or purified plasmacytoid dendritic cells (pDCs) from healthy donors were stimulated with sera from patients with SSc (n=70) or healthy individuals (n=30), together with necrotic or apoptotic cell material. The IFN alpha produced and serum levels of IFN alpha, IFN-inducible protein-10 (IP-10)/chemokine (C-X-C motif) ligand 10, monocyte chemoattractant protein-1 (MCP-1)/(C-C motif) ligand-2 (CCL-2), macrophage inflammatory protein-1 alpha (MIP-1 alpha)/CCL-3 and RANTES/CCL-5 were measured and correlated with the presence of autoantibodies and clinical manifestations in the patients with SSc.
Results Sera from both diffuse SSc and limited SSc contained interferogenic antibodies, which correlated with the presence of anti-ribonucleoprotein and anti-Sjogren syndrome antigen autoantibodies. The pDCs were responsible for the IFN alpha production which required interaction with Fc gamma RII and endocytosis. Increased serum levels of IP-10 were associated with vascular manifestations such as cardiac involvement (p=0.027) and pulmonary arterial hypertension (p=0.036). Increased MCP-1 or IFN alpha serum levels were associated with lung fibrosis (p=0.019 and 0.048, respectively). Digital ulcers including digital loss were associated with increased serum levels of IFN alpha (p=0.029).
Conclusion An activated type I IFN system previously seen in several other systemic autoimmune diseases is also present in SSc and may contribute to the vascular pathology and affect the profibrotic process.
{Author Address}: Uppsala Univ, Dept Med Sci, Uppsala, Sweden; Uppsala Univ, Dept Med Sci, Uppsala, Sweden; Wyeth AB, Solna, Sweden; Uppsala Univ, Dept Med Sci, Uppsala, Sweden; Uppsala Univ, Dept Med Biochem &amp; Microbiol, Uppsala, Sweden; Uppsala Univ, Dept Med Sci, Uppsala, Sweden; Uppsala Univ, Dept Med Biochem &amp; Microbiol, Uppsala, Sweden; Swedish Univ Agr Sci, Dept Biomed Sci &amp; Vet Publ Hlth, Uppsala, Sweden; Uppsala Univ, Dept Med Sci, Uppsala, Sweden
{Database Provider}: Web of Science SCI
{Language}: English
{Country}: Sweden; Sweden; Sweden; Sweden

{Reference Type}: Journal Article
{Author}: Farago, B.; Magyari, L.; Safrany, E.; Csoengei, V.; Jaromi, L.; Horvatovich, K.; Sipeky, C.; Maasz, A.; Radics, J.; Gyetvai, A.; Szekanecz, Z.; Czirjak, L.; Melegh, B.
{Year}: 2008
{Title}: Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis
{Tag}: 0
{Star}: 0
{Journal}: ANNALS OF THE RHEUMATIC DISEASES
{Volume}: 67
{Issue}: 2
{Pages}: 248-250
{ISBN/ISSN}: 0003-4967
{Keywords}: AUTOIMMUNE INFLAMMATION; DISEASE; IL-23; ASSOCIATION
{Abstract}: Objectives: Recently, an association was found between Crohn's disease and the interleukin-23 receptor (IL-23R) gene. Since the IL-23/IL-17 pathway is known to associate with other autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc), we hypothesised that IL-23R could be a shared susceptibility gene.
Methods: Groups of patients with rheumatoid arthritis (n = 412), systemic sclerosis (n = 224), Crohn's disease (n = 190) and healthy controls (n = 220) were genotyped for rs10889677 (exon-3' UTR C2370A), rs2201841, and rs1884444 variants; the first two have been shown to confer risk for Crohn's disease.
Results: We observed an increased prevalence of the homozygous rs10889677 AA and homozygous rs2201841 CC genotypes both in the Crohn's disease and in the RA groups as compared to the controls (12.1%, 11.9% vs 5.91%, p, &lt; 0.05; and 13.2%, 13.1% vs 5.91%, p, 0.05), but not in the SSc patients. Logistic regression analysis revealed that bearing these alleles represent risk for the development of rheumatoid arthritis (chi(2) = 5.58, p = 0.018, OR = 2.15, 95% CI 1.14 - 4.06 for rs10889677; and chi(2) = 7.45, p = 0.006, OR = 2.40, 95% CI 1.28-4.51 for rs2201841). The rs1884444 allele, which has been previously reported as neutral for development of Crohn's disease, was also found neutral for all studied groups in the present study.
Conclusions: The data reported here provide direct evidence that some allelic variants or haplogroups of IL-23R represent independent risk factors for rheumatoid arthritis as well as Crohn's disease, but not for scleroderma.
{Author Address}: Univ Pecs, Dept Med Genet &amp; Child Dev, H-7624 Pecs, Hungary; Univ Pecs, Dept Med Genet &amp; Child Dev, H-7624 Pecs, Hungary; Univ Pecs, Dept Med Genet &amp; Child Dev, H-7624 Pecs, Hungary; Univ Pecs, Dept Med Genet &amp; Child Dev, H-7624 Pecs, Hungary; Univ Pecs, Dept Med Genet &amp; Child Dev, H-7624 Pecs, Hungary; Univ Pecs, Dept Med Genet &amp; Child Dev, H-7624 Pecs, Hungary; Univ Pecs, Dept Med Genet &amp; Child Dev, H-7624 Pecs, Hungary; Univ Pecs, Dept Med Genet &amp; Child Dev, H-7624 Pecs, Hungary; Univ Pecs, Dept Immunol &amp; Rheumatol, Pecs, Hungary; Debrecen Univ Med, Dept Internal Med 3, Immunol Lab, H-4012 Debrecen, Hungary; Hlth Sci Ctr, Debrecen, Hungary; Debrecen Univ Med, Dept Internal Med 3, Div Rheumatol, H-4012 Debrecen, Hungary; Hlth Sci Ctr, Debrecen, Hungary; Univ Pecs, Dept Immunol &amp; Rheumatol, Pecs, Hungary; Univ Pecs, Dept Med Genet &amp; Child Dev, H-7624 Pecs, Hungary
{Database Provider}: Web of Science SCI
{Language}: English
{Country}: Hungary; Hungary; Hungary; Hungary; Hungary

{Reference Type}: Journal Article
{Author}: Kobayashi, Donald Y.; Crouch, Jo Anne
{Year}: 2009
{Title}: Bacterial/Fungal Interactions: From Pathogens to Mutualistic Endosymbionts
{Tag}: 0
{Star}: 0
{Journal}: ANNUAL REVIEW OF PHYTOPATHOLOGY
{Volume}: 47
{Pages}: 63-82
{ISBN/ISSN}: 0066-4286
{Keywords}: ARBUSCULAR MYCORRHIZAL FUNGI; BROWN BLOTCH DISEASE; PSEUDOMONAS-FLUORESCENS PF-5; CANDIDATUS GLOMERIBACTER GIGASPORARUM; BIOLOGICAL-CONTROL ACTIVITY; MUSHROOM AGARICUS-BISPORUS; SUGAR-BEET RHIZOSPHERE; ENZYMOGENES STRAIN C3; SUMMER PATCH DISEASE; III SECRETION SYSTEM; intracellular; biological control; bacterial diseases; endosymbiosis; antibiosis
{Abstract}: A fundamental issue in biology is the question of how bacteria initiate and maintain pathogenic relationships with eukaryotic hosts. Despite billions of years of coexistence, far less is known about bacterial/fungal interactions than the equivalent associations formed by either of these types of microorganisms with higher eukaryotes. This review highlights recent research advances in the field of bacterial/fungal interactions, and provides examples of the various forms such interactions may assume, ranging from simple antagonism and parasitism to more intimate associations of pathogenesis and endosymbiosis. Information derived from the associations of bacteria and fungi in the context of natural and agronomic ecosystems is emphasized, including interactions observed from biological control systems, endosymbiotic relationships, diseases of cultivated mushrooms, and model systems that expand our understanding of human disease. The benefits of studying these systems at the molecular level are also emphasized.
{Author Address}: Rutgers State Univ, Sch Environm &amp; Biol Sci, Dept Plant Biol &amp; Pathol, New Brunswick, NJ 08901 USA; Rutgers State Univ, Sch Environm &amp; Biol Sci, Dept Plant Biol &amp; Pathol, New Brunswick, NJ 08901 USA
{Database Provider}: Web of Science SCI
{Language}: English
{Country}: USA