Circulating and Intragraft Donor (HLA)-Specific B Cells Drive Allograft Rejection After Kidney Transplantation
1Vall d'Hebron Research Institute (VHIR), Barcelona, Spain, 2Vall d'Hebron University Hospital, Barcelona, Spain, 3Bellvitge University Hospital, Barcelona, Spain, 4Vall d'Heron University Hospital, Barcelona, Spain
Meeting: 2022 American Transplant Congress
Abstract number: 1231
Keywords: B cells, Histology, Kidney transplantation, Rejection
Topic: Basic Science » Basic Science » 04 - B-cell / Antibody /Autoimmunity
Session Information
Session Name: B-cell / Antibody /Autoimmunity
Session Type: Poster Abstract
Date: Monday, June 6, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Besides donor-specific antibodies (DSA), circulating donor(HLA)-specific memory B cells (mBc) have also shown to play a deleterious role driving antibody-mediated rejection (ABMR) in kidney transplant patients. The ubiquitous capacity of allo-specific B cells to circulate through the bloodstream but also infiltrating kidney allografts forming organized tertiary lymphoid structures (TLO), seems to be key for both optimal antigen presentation and DSA production. Here, we characterized cellular immune infiltrates including bulk T, B cells, plasma cells and TLOs-like structures directly within kidney allografts undergoing distinct types of rejections (ABMR, TCMR and Mixed), as well as alloreactive B cells with donor(HLA)-antigen specificity using novel (HLA)monomer-based immune technology to determine distinct graft outcomes.
*Methods: In a cohort of 122 consecutives for cause biopsies showing ABMR (n=48), TCMR (n=41), Mixed (n=17) and 20 pristine kidney biopsies, we examined by immunohistochemistry and digital microscopy the presence of (CD20+) B cells, (CD4+) T helper cells, (CD138+) plasma cells and TLOs enriched aggregates of CD4+CXCR5+, CD20+ with active proliferation (Ki67+). In biopsies showing (CD20+)B-cell clusters, we characterized the presence of donor(HLA)-specific B cells. In parallel, circulating donor(HLA)-specific mBc were also monitored.
*Results: While T cells and Plasma cell infiltrates were more frequent in TCMR or ABMR/Mixed rejection, respectively, 80/106 (80%) of rejecting biopsies displayed graft-infiltrating B cells, regardless the type of rejection (ABMR, TCMR, Mixed) (P=NS). Notably, patients with infiltrating B cells and plasma cells displayed significant worse graft survival (log rank= 0.042 and 0.016, respectively). In 50% of biopsies with B-cell infiltrates, regardless the rejection type, B cells were found to cluster forming TLOs-like structures. Interestingly, within most B-cell clusters donor(HLA)-specific B cells were clearly detected, which paralleled those detected in peripheral blood.
*Conclusions: Our study highlights the ubiquity of donor(HLA)-specific B cells during allograft rejection in kidney transplant patients, which seem to be key to orchestrate graft rejection.
To cite this abstract in AMA style:
Torija A, Bolaños N, Donadeu L, Meneghini M, Torres I, Gabaldon A, Gomà M, Crespo E, Moreso F, Bestard O. Circulating and Intragraft Donor (HLA)-Specific B Cells Drive Allograft Rejection After Kidney Transplantation [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/circulating-and-intragraft-donor-hla-specific-b-cells-drive-allograft-rejection-after-kidney-transplantation/. Accessed May 6, 2025.« Back to 2022 American Transplant Congress