Análisis de los anticuerpos anti-HLA de unión al complemento y la supervivencia del trasplante renal

Résumé

HLA molecules are highly polymorphic molecules and represent an important challenge to consider in the compatibility of kidney transplantation, due their recognition, by the recipient's immune system, can lead to the formation of donorspecific antibodies (DSA), which leads to responses strong and long lasting with detrimental results in renal graft survival. Antibody-mediated rejection (AMR) constitutes one of the most important challenges in the context of kidney transplantation, since the binding of DSA to the graft triggers the activation of the complement cascade, which leads to the loss of the transplant. On the other hand, the capacity of complement activation by the DSA varies significantly according to its affinity to bind to the C1q molecule, the first step of this lytic pathway. However, it has been discussed whether the presence of DSA that does not have complement-fixing capacity could not lead to rejection of the transplanted organ. OBJECTIVE Our objective was to determine whether the categorization of DSA according to their ability to bind complement molecules could be a useful tool in post-kidney transplant follow-up. For this, the DSA evaluation was carried out to establish if there is a possible association between the presence of non-complement fixing DSA and renal graft survival, as well as, an association of complement-fixing DSA and the loss of the kidney graft. MATERIALS AND METHODS Our study included 245 transplant patients over a 5-year period at the Virgen de las Nieves University Hospital (HUVN) in Granada, Spain. In 26 patients the presence of DSA was found. Of these, 17 patients (6.9%) with non-complement-fixing DSA and 9 patients (3.7%) with complement-fixing DSA. RESULTS The results of our study demonstrated a statistically significant association between the frequency of rejection events and the presence of DSA with the ability to bind complement molecules. On the other hand, when the DSA did not have the ability to fix complement, this was associated with significantly fewer rejection events. Therefore, we found that the categorization of DSA according to their ability to bind complement provides added value in the early detection of possible renal graft injury. Renal graft survival rates were significantly decreased in those patients who developed DSA with complement-fixing ability. However, they remained similar between patients who did not develop DSA and those who developed DSA without complement-binding ability. Our results also demonstrated that the presence of DSA with the ability to bind complement molecules is strongly associated with kidney graft failure and loss when compared to patients who developed DSA without complement binding ability. CONCLUSIONS Our results suggest that detection of complement binding capacity by DSA could be used as a prognostic marker to predict AMR outcome and graft survival in DSApositive kidney transplant patients.