RESUMEN
INTRODUCTION: Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition. METHODS: A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays. RESULTS: A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (P(MH) = 0.041, OR = 0.88, CI 95% 0.78-0.99) and recessive (P(MH) = 3.40E-03, OR = 0.53, CI 95% 0.35-0.80) models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis. CONCLUSIONS: Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA.
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Arteritis de Células Gigantes/genética , Interleucina-33/genética , Alelos , Estudios de Casos y Controles , Estudios de Cohortes , Susceptibilidad a Enfermedades , Femenino , Redes Reguladoras de Genes , Sitios Genéticos , Genotipo , Arteritis de Células Gigantes/patología , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Masculino , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Receptores de Superficie Celular/genética , Factores de RiesgoRESUMEN
OBJECTIVES: The Xq28 region, containing IRAK and MECP2, represent a common susceptibility locus for a high number of autoimmune diseases. Our aim in the present study was to evaluate the influence of the IRAK1 and MECP2 autoimmunity-associated genetic variants in the giant cell arteritis (GCA) susceptibility and its clinical subphenotypes. METHODS: We analysed a total of 627 female biopsy-proven GCA patients and 1,520 female healthy controls of Spanish Caucasian origin. Two polymorphisms, rs1059702 and rs17345, located at IRAK1 and MECP2, respectively, were genotyped using TaqMan® allelic discrimination assays. RESULTS: No association with any of the analysed polymorphisms was evident when genotype and allele frequencies were compared between GCA patients and controls (rs1059702: allelic p-value=0.699, OR=0.96, CI 95% 0.80-1.17; rs17435: allelic p-value=0.994, OR=1.00, CI 95% 0.84-1.19). Likewise, the subphenotype analysis yield similar negative results. CONCLUSIONS: We have assessed for the first time the possible role of IRAK1 and MECP2 autoimmune disease-associated polymorphisms in GCA. Our data suggest that IRAK1 rs1059702 and MECP2 rs17435 genetic variants do not play a significant role in GCA susceptibility or severity.
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Arterias/patología , Autoinmunidad/genética , Arteritis de Células Gigantes , Quinasas Asociadas a Receptores de Interleucina-1/genética , Proteína 2 de Unión a Metil-CpG/genética , Anciano , Biopsia , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Arteritis de Células Gigantes/epidemiología , Arteritis de Células Gigantes/genética , Arteritis de Células Gigantes/patología , Humanos , Polimorfismo de Nucleótido Simple , España/epidemiología , Población Blanca/genéticaRESUMEN
OBJECTIVE: To evaluate systemic involvement in primary SS in a large cohort of Spanish patients using the EULAR-SS disease activity index (ESSDAI) definitions. METHODS: Systemic involvement was characterized using ESSDAI definitions for the 10 clinical domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system and muscular). ESSDAI scores at diagnosis, during follow-up and cumulated at the last visit were calculated. RESULTS: The cohort consisted of 921 patients. After a mean follow-up of 75 months, 77 (8%) patients still had an ESSDAI score of zero at the last visit. Organ by organ, the percentage of patients who developed activity during the follow-up (ESSDAI score ≥ 1 at any time) ranged between 1.4% and 56%, with articular, pulmonary and peripheral neurological involvement being the most common. Logistic multivariate regression analysis showed the following features at diagnosis and had the closest association with systemic activity (statistically significant independent variables in at least two domains): cryoglobulinaemia in five domains; anaemia, lymphopenia and low C3 levels in three domains each and age <35 years in two domains. Sicca features, ANA and RF at diagnosis were not associated with a higher cumulated activity score in any clinical domain. CONCLUSION: Primary SS is undeniably a systemic disease, with the joints, lungs, skin and peripheral nerves being the most frequently involved organs. Cytopenias, hypocomplementaemia and cryoglobulinaemia at diagnosis strongly correlated with higher cumulated ESSDAI scores in the clinical domains. Clinically the ESSDAI provides a reliable picture of systemic involvement in primary SS.
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Sistema de Registros , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/epidemiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Artropatías/epidemiología , Enfermedades Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Análisis de Regresión , Índice de Severidad de la Enfermedad , Enfermedades de la Piel/epidemiología , España/epidemiologíaRESUMEN
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