Phospho ERK
6.2 Développement d'un substitut aux Igl
Les présents travaux ont permis de mieux comprendre certains des mécanismes d'actions des IglV sur les lymphocytes B et de proposer de nouvelles cibles afin de développer des substituts. Ainsi, un anticorps dirigé contre les phb pourrait avoir un effet
anti-inflammatoire dans certaines maladies. En plus d'être internalise et d'ainsi compétitionner avec des autoantigènes pour être présentés sur le CMH de classe II, un anticorps dirigé contre le CD91 pourrait induire une signalisation par ce récepteur et reproduire une partie de l'effet des IglV. De plus, des anticorps dirigés contre les phb ou le CD91 pourraient être utilisés à des doses beaucoup plus faibles que les IglV tout en reproduisant le même effet car il est probable que seule une faible fraction des IglV est capable d'interagir avec les phb ou le CD91. fl pourrait être aussi envisageable de cibler ces protéines avec d'autres approches que l'utilisation d'anticorps. Par exemple l'identification de petites molécules chimiques capables d'interagir avec le CD91 et ainsi induire une signalisation similaire à celle induite par les IgPV pourrait être envisagée et pourrait représenter des substituts facilement disponibles en quantité suffisante pour leur utilisation à grande échelle.
Certains substituts ont déjà montré leur efficacité dans des modèles murins de maladies auto-immunes Ainsi, une étude a montré qu'il serait possible d'envisager de procéder au traitement ex vivo des cellules dendritiques par un anticorps dirigé contre PIR-A comme thérapie de remplacement aux IglV chez des patients souffrant d'ITP68. Il a
aussi été démontré que des fragments Fc recombinants sialylés sont capables de reproduire l'effet des IglV dans un modèle murin d'arthrite rhumatoïde205. De plus, un inhibiteur de
Syk a été démontré pour augmenter le niveau des plaquettes sanguines chez 50 % des patients atteints dTTP dans une étude clinique phase II °6.
La complexité des mécanismes d'action des IglV rend difficile l'élaboration d'un substitut capable de reproduire la totalité de leurs effets. Ainsi, bien qu'il semble peu probable de parvenir à développer un substitut aux IglV capable de reproduire la totalité de leurs effets immunomodulateurs, il est pensable de pouvoir parvenir à soutenir la demande continuellement croissante en utilisant une combinaison de plusieurs substituts. Cependant, aucun substitut n'a encore fait ses preuves lors d'essais cliniques phase III et IV. Il est donc important de poursuivre la recherche sur les mécanismes d'action des IglV et le développement de produits substituts.
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