Antibody-Mediated Rejection Is Associated With Higher Serum Levels of CXCL13 and CCL21 in Renal Transplant Patients and Altered By Bortezomib/Rituximab Treatment
1Nephrology, Charité
Universitätsmedizin Berlin, Berlin, Germany
2Institute of Transplant Immunology, IFB-Tx, MHH, Hannover, Germany.
Meeting: 2015 American Transplant Congress
Abstract number: C19
Keywords: B cells, Graft failure, Lymphocytes
Session Information
Session Name: Poster Session C: Antigen Presenting Cells in Alloimmune Responses/B Cells and Antibody in Alloimmune Responses
Session Type: Poster Session
Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
In renal transplant patients (pts), B- and plasma cells (PC) are crucial for donor-specific HLA antibody (DSA) formation. The underlying mechanisms, which lead to B cell migration into the allograft are not fully understood in the transplant context. Chemokines, like CXCL13 and its receptor CXCR5 are known to play a key role in B cell trafficking to lymphatic tissue (LT). For T cells, CCR7 and its ligands CCL19, 21 are responsible for recruitment into LT. However, limited data exist about these dynamics in antibody-mediated rejection (AMR) with B- and PC specific therapy.
The aim of this prospective study was to investigate serum chemokines, in particular CXCL13 and CCL21 and their diversification in renal transplant pts undergoing AMR therapy including rituximab and bortezomib (BZ) with adequate control pts.
In total, 34 pts participated and were divided into three groups. 16 pts had DSA and biopsy proven AMR according to BANFF-criteria (AMR-group). Therapy included steroids, plasmapheresis, IVIG, 1cycle of BZ and or 500mg rituximab. 10 pts had confirmed DSA only, but stable renal function and no signs of AMR (DSA-group). The control group consists of 10 pts with stable graft function and no evidence for DSA or rejection. CXCL13 and CCL21 were quantified along with 15 other chemokines including CXCL5, 12, CCL13 with multiplex technique at baseline, month (Mo) 3 and 12 after study inclusion.
At baseline, AMR group demonstrated significant higher levels of CXCL13 and CCL21 compared to DSA group (577 vs 77 and 760 vs 641; pg/ml, p=0.02) or control group. Interestingly, levels of CXCL12 and 5 were lower in contrast to DSA (3414 vs 4230 pg/ml; p=0.04 and 1098 vs 1983pg/ml; p=ns) or control group. 12 Mo after AMR therapy, CXCL13 (276pg/ml) and CCL21 (672pg/ml) showed sustained elevated levels. Noticeable, CCL13 and CXCL5 were affected by AMR therapy leading to lower levels.
The present study observed a profound and sustained elevation of CXCL13 and CCL21 values in patients with diagnosed AMR in contrast to DSA- or control groups. Interestingly, despite B- cell and PC directed therapy, neither CXCL13 nor CCL21 levels were reduced significantly. In contrast, reduced CXCL12 and 5 levels in AMR pts indicate a specific chemokine repertoire associated with pathology, which might help to stratify patients by risk to develop future AMR.
To cite this abstract in AMA style:
Duerr M, Daemen K, Keil J, Budde K, Falk C. Antibody-Mediated Rejection Is Associated With Higher Serum Levels of CXCL13 and CCL21 in Renal Transplant Patients and Altered By Bortezomib/Rituximab Treatment [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/antibody-mediated-rejection-is-associated-with-higher-serum-levels-of-cxcl13-and-ccl21-in-renal-transplant-patients-and-altered-by-bortezomibrituximab-treatment/. Accessed May 19, 2025.« Back to 2015 American Transplant Congress