ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 777

Influence of the IL17A Locus in Giant Cell Arteritis Susceptibility

Javier Martin1, Ana Márquez2, José Hernández-Rodríguez3, Maria C. Cid4, Roser Solans5, Santos Castañeda6, Inmaculada C. Morado7, Javier Narváez8, Victor M. Martinez-Taboada9, Norberto Ortego-Centeno10, Bernardo Sopeña11, Jordi Monfort12, Maria Jesus Garcia-Villanueva13, Luis Caminal-Montero14, Eugenio De Miguel15, Ricardo Blanco16, Øyvind Palm17, Øyvind Molberg18, Joerg Latus19, Niko Braun19, Frank Moosig20, Torsten Witte21, Lorenzo Beretta22, Alessandro Santaniello23, Giulia Pazzola24, Luigi Boiardi25, Carlo Salvarani26 and Miguel A. Gonzalez-Gay9, 1Immunology, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Armilla (Granada), Spain, 2Instituto de Parasitologia y Biomedicina López-Neyra (IPBLN-CSIC) and Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain, 3Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, 4Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036- Barcelona, Spain, 5Autoimmune Systemic Diseases Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain, 6Department of Rheumatology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain, 7Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain, 8Rheumatology, Hospital Universitario de Bellvitge. Barcelona. Spain, Barcelona, Spain, 9Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain, 10Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain, 11Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo, Vigo, Spain, 12Department of Rheumatology, Grup de recerca cel•lular en inflamació i cartílag. IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain, 13Department of Rheumatology, Hospital Ramón y Cajal, Madrid, Spain, 14Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain, 15Department of Rheumatology, Hospital Universitario La Paz, Madrid, Spain, 16Hospital Marques de Valdecilla, Santander, Spain, 17Department of Rheumatology, Oslo University Hospital and University of Oslo, Oslo, Norway, 18Department of Rheumatology, Oslo University Hospital Rikshospitalet, Oslo, Norway, 19Department of Internal Medicine, Division of Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany, 20Department of Clinical Immunology and Rheumatology, University of Luebeck, Bad Bramstedt, Germany, 21Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany, 22Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy, 23Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy, 24Rheumatology Unit, Arcispedale S Maria Nuova, Reggio Emilia, Italy, 25Unita` Operativa di Reumatologia, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy, 26Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Vasculitis

Session Type: Abstract Submissions (ACR)

Background/Purpose: A recent study has showed that the number of Th17 lymphocytes is significantly increased in patients with GCA, resulting in an imbalance between Th17 and regulatory T cells. In addition, an increased expression of IL-17A, a Th17 cytokine leading to pro-inflammatory responses, has been detected in temporal artery samples from GCA patients. Considering the proposed crucial role of Th17 cells in this vasculitis, we aimed to assess whether polymorphisms at the IL17A gene are involved in the genetic predisposition to GCA and its main clinical subgroups.

Methods: We carried out a large meta-analysis including a total of 1,266 biopsy-proven GCA patients and 3,779 healthy controls from four European populations (Spanish cohort: 931 cases and 1,845 controls, German cohort: 74 cases and 480 controls, Italian cohort: 178 cases and 1,175 controls, and Norwegian cohort: 83 cases and 279 controls). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), which tag over 86% of the variability of this locus, were genotyped using TaqMan® assays. Allelic combination and dependency tests were also performed.

Results: In the pooled analysis, two of the five analyzed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR= 1.17 [1.06-1.29]; rs7747909: PMH=8.49-03, OR= 1.15 [1.04-1.27]). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR= 1.11 [1.00-1.23]). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harboring the risk alleles better explained the observed association than the polymorphisms independently (likelihood P-value<10-05).

Conclusion: Our study provides clear evidence of the role of IL17A as a novel genetic risk locus for GCA, thus contributing to the advance in the knowledge of the genetic network underlying this vasculitis susceptibility.

Disclosure:

J. Martin,
None;

A. Márquez,
None;

J. Hernández-Rodríguez,
None;

M. C. Cid,
None;

R. Solans,
None;

S. Castañeda,
None;

I. C. Morado,
None;

J. Narváez,
None;

V. M. Martinez-Taboada,
None;

N. Ortego-Centeno,
None;

B. Sopeña,
None;

J. Monfort,
None;

M. J. Garcia-Villanueva,
None;

L. Caminal-Montero,
None;

E. De Miguel,
None;

R. Blanco,
None;

Palm,
None;

Molberg,
None;

J. Latus,
None;

N. Braun,
None;

F. Moosig,
None;

T. Witte,
None;

L. Beretta,
None;

A. Santaniello,
None;

G. Pazzola,
None;

L. Boiardi,
None;

C. Salvarani,
None;

M. A. Gonzalez-Gay,
None.

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