Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis.

OBJECTIVE: To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). METHODS: Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. RESULTS: The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). CONCLUSIONS: Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

A case-control study suggests that the CCR6 locus is not involved in the susceptibility to giant cell arteritis.

OBJECTIVES: Polymorphisms of the CC chemokine receptor 6 (CCR6) gene have been recently reported to be associated with a number of autoimmune diseases. We aimed to investigate the possible influence of CCR6 rs3093024 gene variant in the susceptibility to and clinical expression of GCA. METHODS: The CCR6 polymorphism rs3093024 was genotyped in a total of 463 Spanish patients diagnosed with biopsy-proven GCA and 920 healthy controls using a TaqMan® allelic discrimination assay. PLINK software was used for the statistical analyses. RESULTS: No significant association between this CCR6 variant and GCA was observed (p=0.42, OR=0.94, CI95% 0.79-1.10). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischaemic manifestations or irreversible occlusive disease, no statistical significant difference was detected either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. CONCLUSIONS: Our results suggest that the CCR6 rs3093024 polymorphism may not play a relevant role in the GCA pathophysiology.

[Analysis of a series of 55 patients with biopsy proven giant cell temporal arteritis]. / Análisis de una serie de 55 pacientes con arteritis de células gigantes confirmada por biopsia.

INTRODUCTION: Our main aim with this study is to establish the epidemiologic and clinical features, treatment response and complications of a group composed of 55 patients with biopsy proven temporal arteritis in a local hospital. MATERIAL AND METHODS: Retrospective study based on clinical records revision of patients diagnosed of giant cell arteritis (GCA) made by temporal artery biopsy between 1989 and 2001. RESULTS: The approximated annual incidence of GCA in our area is 4.1 cases per 100,000 persons over the age of 50. The mean age at diagnostic was 74 years and the 78,2% were women. The most common symptom at diagnostic was headache (81.5%) followed by systemic manifestations (74.1%) and later we found jaw claudication (32,7%), visual impairment (30.2%), isquemic manifestations (17%). Polymyalgia rheumatica was associated to GCA in 49.1% of cases. The temporal artery explorations was abnormal in the 76.9% of patients. The mean initial dose of corticoids was 69 mg prednisone per day, with a half dose reduction time of .5 months. In spite of that, 24,1% of patients relapsed during the first year. The 38% of patients did some complications during the corticosteroid treatment. The ESR was lower 50 mm in 12.7% of patients; it was anaemia in the 37.7% and thrombocytosis in 32,1%. In these last patients we detected a relation between thrombocytosis and specific visual impairment. CONCLUSIONS: The incidence of GCA in our area is low. The results of our series aren't different from others publicated before in clinical manifestations, there is a prevalence of female sex and there is a relation between specific visual impairment and the presence of thrombocytosis.

Análisis de una serie de 55 pacientes con arteritis de células gigantes confirmada por biopsia / Analysis of a serie of 55 patients with biopsy proven giant cell temporal arteritis

Introducción: Descripción de las características epidemiológicas, clínicas, respuesta al tratamiento y complicaciones de una serie de 55 pacientes con arteritis de células gigantes(ACG) confirmada por biopsia en un hospital comarcal. Material y métodos: Estudio retrospectivo de los pacientes diagnosticados de ACG por biopsia de arteria temporal en el periodo comprendido entre 1989 y 2001 en nuestro centro. Resultados: La incidencia anual aproximada calculada en nuestra área sería de 4,1 casos por 100.000 habitantes mayor de 50 años. La edad media al diagnóstico fue de 74 años y un 78,2 por ciento eran mujeres. El síntoma más frecuente al diagnóstico fue la cefalea (81,5 por ciento), seguido de las manifestaciones sistémicas (74,1 por ciento), a más distancia se encontraba la claudicación mandibular (32,7 por ciento), trastornos visuales (30,2 por ciento), manifestaciones isquémicas (17 por ciento). La polimialgia reumática se asoció a ACG en el 49,1 por ciento. La palpación de arteria temporal fue anormal en el 76,9 por ciento de los pacientes. La dosis media de inicio de tratamiento fue de 69 mg prednisona /dia, con una media de tiempo de reducción a mitad de dosis fue de 3,5 meses. Un 24,1 por ciento de los pacientes presentaron un rebrote durante el primer año. Un 38 por ciento de los pacientes presentaron complicaciones durante el tratamiento corticoideo. La VSG fue inferior a 50 mm en el 12,7 por ciento de los pacientes, existía anemia en el 37,7 por ciento y trombocitosis en el 32,1 por ciento. En estos últimos se detectó una tendencia a la relación con presencia de alteraciones visuales específicas. Conclusiones: La incidencia de ACG en nuestra área estaría dentro de las zonas de baja incidencia. Los resultados de nuestra serie no difieren de otras descritas previamente en la literatura en cuanto a las manifestaciones clínicas de los pacientes, existe un claro predominio del sexo femenino y se detecta una tendencia a la relación de alteraciones visuales específicas con presencia de trombocitosis (AU)