RESUMO
It has been suggested that the R92Q mutation of the tumour necrosis factor receptor superfamily 1A (TNFRS1A) gene may be implicated in different inflammatory disorders. The aim of this study was to establish the role of this mutation as a determinant of Crohn`s disease (CD) susceptibility and/or clinical phenotype. One hundred and sixty-five CD patients and 203 healthy controls were prospectively included. The frequency of individuals carrying the R92Q mutation was similar between CD patients (4.24 percent) and controls (4.43 percent) (OR: 0.95; 95 percent CI = 0.34-2.62). In the genotype-phenotype evaluation, the univariate analysis showed that extra-intestinal manifestations were positively associated with the presence of R92Q mutation (p = 0.025; OR: 5.56; 95 percent CI = 1.04-29.6). In the multivariate analysis, presence of R92Q mutation was independently associated to extra-intestinal manifestations of CD, specially cutaneous manifestations (p = 0.02; OR: 5.17, 95 percent CI = 1.07-24.8). The R92Q mutation of TNFRSF1A gene is not a determinant of CD susceptibility, but contributes to the appearance of extra-intestinal manifestations of the disease.
Se ha sugerido que la mutación R92Q del gen de la super-familia del receptor del factor de necrosis tumoral 1A (TNFRS1A) podría estar relacionada con diversos trastornos inflamatorios. El objetivo de este estudio fue determinar el papel de esta mutación como factor determinante de la susceptibilidad y/o fenotipo clínico de la enfermedad de Crohn (EC). Ciento sesenta y cinco pacientes con EC y 203 controles sanos fueron incluidos de manera prospectiva. La frecuencia de individuos portadores de la mutación R92Q fue similar entre los pacientes con EC (4,24 por ciento) y los controles (4,43 por ciento) (OR: 0,95; 95 por ciento IC = 0,34-2,62). En la evaluación genotipo-fenotipo, el análisis univariado indicó que las manifestaciones extra-intestinales estaban relacionadas con la presencia de la mutación R92Q (p = 0,025; OR: 5,56; 95 por ciento IC = 1,04-29,6). En el análisis multivariado, la presencia de la mutación R92Q estuvo relacionada de manera independiente con las manifestaciones extra-intestinales de la EC, especialmente manifestaciones cutáneas (p = 0,02; OR: 5,17, 95 por ciento IC = 1,07-24,8). La mutación R92Q del gen TNFRSF1A no es un factor determinante de susceptibilidad a EC, pero contribuye a la aparición de manifestaciones extra-intestinales de la enfermedad.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Doença de Crohn/complicações , Doença de Crohn/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Doenças Inflamatórias Intestinais/genética , Dermatopatias/etiologia , Estudos de Casos e Controles , Seguimentos , Fenótipo , Genótipo , MutaçãoRESUMO
Objetivo: determinar si la presencia de valores persistentemente positivos de anticuerpos antifosfolipídicos (AAF) está relacionada con trombosis recurrente en el seguimiento de pacientes con síndrome antifosfolipídico (SAF). Métodos: se analizaron 141 pacientes con SAF (criterios de Sapporo). Los valores de anticoagulante lúpico (AL) y anticuerpos anticardiolipina (AAC) fueron definidos como persistentemente positivos cuando más del 75% de las determinaciones fueron positivas durante el seguimiento (los AAF fueron medidos en cinco o más ocasiones). La trombosis en el seguimiento fue definida como una trombosis recurrente en pacientes con episodios trombóticos previos o nuevos episodios en aquellos pacientes con pérdidas fetales previas. Resultados: ochenta y nueve pacientes presentaban SAF primario, 34 asociado a lupus eritema-toso sistémico (LES), 14 con síndrome similar al lupus, 3 con síndrome de Sjogren y 1 con enfermedad de Beh
Objective: to determine if the presence of persistently positive valúes of antiphospholipid (aPL) antibodies is related with recurrent thrombosis in the follow-up of patíent with antiphospholipid syndrome (APS). Patients and Methods: 141 patients with APS (Sapporo's criteria) were analyzed. Lupus antico-agulant (LAC) valúes and anticardiolipin antibodies (aCL) were defined as persistently positive when more than 75% of determinations were positive during the follow-up (aPL were measured on 5 or more occasions). Thrombosis in the follow-up was defined as a recurrent thrombosis in patient with previous thrombotic events or new events in those patients with previous fetal losses. Results: 89 patients suffered from primary APS, 34 associated to systemic lupus erythematosus (SLE), 14 to SLE-like, 3 to Sjogren's syndrome, and 1 to Behcet's disease. 56% liad a history of thrombosis, 29% of fetal losses, and 15% both thrombosis and fetal losses. Median time of follow-up and between the diagnosis and the last aPL determination was 68 months and 65 months (9-180), respectively. Median of determinations by patient was 8 (5-27). 31 patients suffered from thrombosis in the follow-up, 28 of them in form of recurrent thrombosis. 58 (41%) patients liad persistently positive aPL during follow-up, thus: 23 (39,65%) aCL IgG y LAC, 12 (20,7%) LAC, 8 (13,8%) aCL IgG, 5 (8,6%) aCL IgM, aCL IgG y LAC, 4 (6,9%) aCL IgM, 3 (5,1%) aCL IgG y aCL IgM y 3 (5,1%) aCL IgM y LAC, respectively. Risk for recurrent thrombosis during follow-up was increased in persistently positive aPL patients (OR 3,53; 95% CI 1,53-8,16; p=0,003) compared with transiently positive aPL patients. This higher risk was attributable to persistently positive LA (OR 3,87; 95% CI 1,68-8,91; p=0,002) and persistently positive aCL IgG (OR 2,91; 95% CI 1,25-6,75; p=0,02). The profile of persistently positive aPL related with the appearance of thrombosis during follow-up was the combination of IgG aCL & LA (OR 3,51; 95% CI 1,36-9,09; p=0,01). Conclusions: the risk of thrombosis during follow-up is increased in patients with persistently positive aPL, specially in those with the combination of IgG aCL & LA.