B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization

• DOI: 10.3389/fmed.2021.781239
• Publication Date: 2021-12-16T12:37:18Z
• Authors: David Cucchiari; Valeria Tubita; Jordi Rovira; Maria J. Ramirez-...; Elisenda Banon-Ma...; Marta Lazo-Rodriguez; Natalia Hierro-Ga...; Francesc E. Borràs; Pedro Ventura-Aguiar; Gastón J. Piñeiro; Jaume Martorell; Lluís Peri; Mireia Musquera; Alexandre Hertig; Federico Oppenheimer; Josep M. Campistol; Fritz Diekmann; Ignacio Revuelta
• Keywords: 0301 basic medicine; Medicine (General); B cells; Plasma cells; Cèl·lules B; Trasplantament renal; desensitization; kidney transplantation; exosomes; Desensitization; HLA-incompatibility; Extracellular vesicles (EV); Exosomes; plasma cells; 3. Good health; Kidney transplantation; 03 medical and health sciences; R5-920; Antígens HLA; extracellular vesicles (EV); Energia exosomàtica; Medicine; HLA histocompatibility antigens; Exosomatic energy

Background: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose the study is to evaluate if residual B cell activity after could be estimated by presence circulating cell-derived extracellular vesicles (BEVs). Methods: BEVs were isolated Sepharose-based size exclusion chromatography and defined as CD19+ HLA-II+ vesicles. We analyzed stored serum samples from positive crossmatch LDKT before at first post-transplant biopsy 12-month protocol (n = 11). Control groups formed hypersensitized patients who not submitted 10) low-risk 9). A prospective validation cohort 11 also included analysis cells subpopulations in recipients' blood lymph nodes recovered upon graft implantation, along with desensitization. Results: found out that HLA-II+BEVs dropped significantly relapse later developed ABMR was evident. validated these findings proof-of-concept 6 received same control group 5 recipients. In patients, studied implantation. confirmed significant drop this paralleled reduction CD19+cells nodes, while peripheral cells, change almost undetectable. Conclusions: reflected valid surrogate humoral alloreactivity setting.