RESUMEN
We report the case of a patient with rheumatoid arthritis (RA) who developed a membranous nephropathy (MN) with nephrotic syndrome while receiving etanercept, a fusion protein that binds specifically to TNFalpha and blocks its interaction with TNFalpha receptors. A 62-year-old man with RA treated with etanercept was admitted to our unit in March 2008 because of a full-blown nephrotic syndrome. Renal biopsy showed a typical MN. Since no improvement of proteinuria was observed after withdrawal of etanercept, we administered rituximab (1 g two weeks apart repeated after 6 months). The signs and symptoms of RA improved and proteinuria decreased from 7.2 g/24h to 2.3 g/24h. MN is an immunological glomerulonephritis that may complicate other immune-mediated diseases or may be triggered by a number of drugs. The clinical improvement of both RA and MN after rituximab may indirectly confirm the role of antibodies in the pathogenesis of these diseases, although the mechanisms of action of this drug in immunological disorders remain to be elucidated.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antirreumáticos/efectos adversos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Glomerulonefritis Membranosa/inducido químicamente , Glomerulonefritis Membranosa/tratamiento farmacológico , Inmunoglobulina G/efectos adversos , Factores Inmunológicos/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Etanercept , Humanos , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral , Inducción de Remisión , RituximabRESUMEN
We investigated the role of thrombophilic mutations as possible modifiers of the clinical phenotype in severe factor VII (FVII) deficiency. Among 7 patients homozygous for a cross-reacting material-negative (CRM-) FVII defect (9726+5G>A, FVII Lazio), the only asymptomatic individual carried FV Leiden. Differential modulation of FVII levels by intragenic polymorphisms was excluded by a FVII to factor X (FX) gene haplotype analysis. The coagulation efficiency in the FV Leiden carrier and a noncarrier was evaluated by measuring FXa, FVa, and thrombin generation after extrinsic activation of plasma in the absence and presence of activated protein C (APC). In both patients coagulation factor activation was much slower and resulted in significantly lower amounts of FXa and thrombin than in a normal control. However, more FXa and thrombin were formed in the plasma of the patient carrying FV Leiden than in the noncarrier, especially in the presence of APC. These results were confirmed in FV-FVII doubly deficient plasma reconstituted with purified normal FV or FV Leiden. The difference in thrombin generation between plasmas reconstituted with normal FV or FV Leiden gradually decreased at increasing FVII concentration. We conclude that coinheritance of FV Leiden increases thrombin formation and can improve the clinical phenotype in patients with severe FVII deficiency.