Antígens menors d'histocompatibilitat en el trasplantament al·logènic de progenitors hematopoètics. Modulació de la resposta en funció del genotip CTLA-4

Minor histocompatibility antigens (mHAgs) are peptides derived from polymorphic intracellular proteins that can be recognized in an allogeneic setting by the donor T-lymphocytes leading to the appearance of graft-versus-host disease (GvHD); however, the correlation between mHAgs and this complication is a matter of debate. Polymorphisms on the CTLA-4 gene have been previously associated with autoimmune diseases, predisposition to leukemic relapse, and with GvHD or relapse after allogeneic transplant. There are no studies exploring if these polymorphisms may modulate the ability of the immune system to develop responses in the presence of a specific antigen; and nor studies regarding the effect of CTLA-4 polymorphisms on alloimmune recognition when the allogeneic hematopoietic stem cell transplant (allo-HSCT) is performed with exhaustive T cell depletion through CD34-positive selection (allo- HSCT-CD34), where the immune response will depend on the newly generated T cells from the infused stem. Our hypothesis was that mHAgs disparities have an impact in clinical outcome after allo-HSCT from sibling donor; that the CTLA-4 genotype of the donor may modulate the ability of the allogeneic T lymphocytes to respond in front of mHAg mismatches, even when the graft is T cell depleted Els antigens menors d’histocompatibilitat (AgsmH) son peptids precedents de proteines polimorfiques endogenes que poden ser reconegudes en un context al·logenic pels limfocits T del donant, donant lloc al desenvolupament de malaltia d’empelt contra l’hoste (MECH); tot i aixi, la correlacio entre els AgsmH i l’aparicio d’aquesta complicacio es encara tema de debat. Els polimorfismes del gen CTLA-4, han estat relacionats amb malalties autoimmunitaries, predisposicio a recaigudes de leucemies, i amb MECH i recidives post-trasplantament de progenitors hematopoetics (al·lo-TPH). La hipotesi del present treball es que les disparitats en antigens menors d’histocompatibilitat tenen un impacte en el resultat clinic de trasplantament al·logenic a partir d’un germa HLA-identic; i que el genotip de CTLA-4 dels limfocits T del donant podrien estar modulant la resposta immunitaria davant d’aquestes disparitats, inclus, quan el pacient rep un empelt lliure de limfocits T per seleccio positiva de CD34.