RESUMEN
PURPOSE: Complement regulators control the activated complement system. Defects in this homeostasis can result in tissue damage and autoimmune diseases with a heterogeneity in clinical presentation. Complement factor I (FI), a serine protease, is an important regulator of alternative pathway activation. We report a diagnostic work-up of a patient with relapsing inflammatory mediated meningo-encephalitis. Our work-up revealed a rare genetic factor I (FI) deficiency. So far, all cases of reported complete factor I deficiency have absent serum levels of FI. We present here a unique case of a complete factor I deficiency based on a functional FI defect. METHODS: Complement assays and measurement of FI activity were performed in the patient, her family, factor H-deficient patients, a patient with C3-nephritic factor and 11 healthy controls. Genetic sequencing of the FI coding regions in the patient and her parents was performed. RESULTS: The patient had absent alternative pathway activity with low levels of C3 and normal serum level of FI. The patient's plasma FI did not degrade C3b, with normalisation of C3b degradation after adding purified FI. Mutation analysis of the complement factor I gene revealed two heterozygous mutations (I322T and D506V). CONCLUSION: To our knowledge, this paper describes a complete FI deficiency caused by a defect of FI activity for the first time. Normal FI concentration does not exclude a complete FI defect, additional functional analysis of FI is required in any patient with a defect of complement activation. Recurrent aseptic meningo-encephalitis is a rare clinical presentation of complete FI deficiency.
Asunto(s)
Factor I de Complemento/deficiencia , Factor I de Complemento/genética , Meningitis Aséptica/genética , Meningitis Aséptica/inmunología , Meningoencefalitis/genética , Meningoencefalitis/inmunología , Activación de Complemento/genética , Activación de Complemento/inmunología , Factor I de Complemento/fisiología , Hemólisis/genética , Hemólisis/inmunología , Humanos , Meningitis Aséptica/metabolismo , Meningoencefalitis/metabolismo , Recurrencia , Análisis de Secuencia de ADNRESUMEN
Although TauA shares few common characteristics with other known periplasmic binding protein, TauA is a putative periplasmic binding protein, part of tauABCD gene cluster involved in sulfonate transport in sulphate starvation condition. This protein was expressed in E. coli BL 21 and purified before to assess its binding functionalities. Measurement of K (d) value (mean 11.3 nM) by binding/dialysis studies revealed high affinity and specificity with taurine and also indicated that TauA possessed a unique binding site for its ligand. Comparisons with other periplasmic binding proteins suggests TauA plays a major role in ABC transport system and could be ideal candidate to serve as taurine catcher in biological fluids.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/química , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Transportadoras de Casetes de Unión a ATP/fisiología , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Proteínas de Escherichia coli/fisiología , Regulación Bacteriana de la Expresión Génica , Cinética , Ligandos , Proteínas de Transporte de Membrana/química , Proteínas de Unión Periplasmáticas/metabolismo , Plásmidos/metabolismo , Unión Proteica , Desnaturalización Proteica , Pliegue de Proteína , Taurina/químicaRESUMEN
A serine protease activity was detected in aqueous peanuts seeds extracts, partially purified and characterized as a thiol-dependent serine protease. The potential role of this proteolytic activity on allergic reaction to peanuts was prospected through complement activation studies in human plasma and serum, and MDCK cells to investigate a possible occludin degradation in tight junctions. The peanut protease activity induced the production of anaphylatoxins C3a and C5a, and of the terminal membrane attack complex SC5b-9 whatever the complement activation pathway. The protease activity was also involved in the partial digestion of occludin within tight junctions, with for result, an increase of the epithelial permeability to antigen absorption.