Non-HLA Antibodies in Kidney Transplantation: Immunity and Genetic Insights.

The polymorphic human leukocyte antigen (HLA) system has been considered the main target for alloimmunity, but the non-HLA antibodies and autoimmunity have gained importance in kidney transplantation (KT). Apart from the endothelial injury, secondary self-antigen exposure and the presence of polymorphic alloantigens, respectively, auto- and allo- non-HLA antibodies shared common steps in their development, such as: antigen recognition via indirect pathway by recipient antigen presenting cells, autoreactive T cell activation, autoreactive B cell activation, T helper 17 cell differentiation, loss of self-tolerance and epitope spreading phenomena. Both alloimmunity and autoimmunity play a synergic role in the formation of non-HLA antibodies, and the emergence of transcriptomics and genome-wide evaluation techniques has led to important progress in understanding the mechanistic features. Among them, non-HLA mismatches between donors and recipients provide valuable information regarding the role of genetics in non-HLA antibody immunity and development.

Immunosuppression as a Risk Factor for De Novo Angiotensin II Type Receptor Antibodies Development after Kidney Transplantation.

(1) Background: Angiotensin II type I receptor antibodies (AT1R-Ab) represent a topic of interest in kidney transplantation (KT). Data regarding the risk factors associated with de novo AT1R-Ab development are lacking. Our goal was to identify the incidence of de novo AT1R-Ab at 1 year after KT and to evaluate the risk factors associated with their formation. (2) Methods: We conducted a prospective cohort study on 56 adult patients, transplanted between 2018 and 2019. Recipient, donor, transplant, treatment, and complications data were assessed. A threshold of >10 U/mL was used for AT1R-Ab detection. (3) Results: De novo AT1R-Ab were observed in 12 out of 56 KT recipients (21.4%). The median value AT1R-Ab in the study cohort was 8.5 U/mL (inter quartile range: 6.8-10.4) and 15.6 U/mL (10.8-19.8) in the positive group. By multivariate logistic regression analysis, induction immunosuppression with anti-thymocyte globulin (OR = 7.20, 95% CI: 1.30-39.65, p = 0.02), maintenance immunosuppression with immediate-release tacrolimus (OR = 6.20, 95% CI: 1.16-41.51, p = 0.03), and mean tacrolimus trough level (OR = 2.36, 95% CI: 1.14-4.85, p = 0.01) were independent risk factors for de novo AT1R-Ab at 1 year after KT. (4) Conclusions: De novo AT1R-Ab development at 1 year after KT is significantly influenced by the type of induction and maintenance immunosuppression.