Abstracts
Résumé
Au cours d’une même maladie auto-immune, la réponse B auto-immunitaire est diverse. Cette diversité n’est probablement pas présente à l’origine du processus auto-immun, mais semble plutôt survenir durant l’évolution de la maladie. Elle est une conséquence d’un processus d’extension épitopique au cours duquel l’immunité se développe séquentiellement d’un déterminant antigénique B à un autre. En outre, les anticorps spécifiques d’un antigène donné peuvent réagir avec des structures moléculaires apparemment dissemblables, portant (réactivité croisée) ou ne portant pas (polyspécificité) un motif antigénique commun. Ces phénomènes participent à la constitution du répertoire des auto-anticorps au cours des maladies auto-immunes. Ils jouent un rôle important dans l’initiation et le maintien des réponses auto-immunes, ainsi que dans la pathogénie des maladies. Ils contribuent aussi à établir un profil de réponse auto-anticorps caractéristique d’une même maladie auto-immune ou d’un sous-groupe de maladie. Différentes stratégies méthodologiques ont été récemment mises en oeuvre pour explorer le répertoire des auto-anticorps et proposer des approches diagnostiques fondées sur l’analyse non plus d’un seul couple auto-antigène/auto-anticorps, mais sur des profils de modification du répertoire.
Summary
Autoimmune response is diverse. This diversity is thought not to take place at the beginning of the autoimmune process but to occur as the disease evolves. It is mainly the consequence of the so-called epitope-spreading phenomenom and of the cross-reactivity of antibodies. Analysing autoantibody repertoire constitutes a powerful means to understand physiopathological processes at work in various diseases, mainly autoimmune diseases. In particular this analysis opens the way to precisely identify autoantigens and their changes in various pathological situations, and allows providing new biological markers in chronic inflammatory diseases. New methodologies have recently emerged for the analysis of the autoantibody repertoire in a given individual. They propose diagnostic approaches no more related upon few markers but founded upon analysis of global changes of the antibody repertoire. They belong to methodologies called target-oriented proteomics. Their common feature is to isolate autoantigens by means of affinity chromatography based upon antibody /antigen reactions. Autoantibodies to be studied interact with a protein substratum susceptible to include autoantibody targets. These interactions take place on solid macro- or microsurfaces, i.e. membrane filters or chips. Several strategies can be used for locating the specific autoantibody/autoantigen complexes and for identifying behind autoantigens. In this paper three approaches, namely, the recombinant protein chips, the SELDI techniques and the 2-D gel electrophoresis linked to mass spectrometry are described and compared.
Appendices
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