B Cell Derived Exosomes Are Associated with Antibody Mediated Rejection in Kidney Transplant Recipients Desensitized for a Positive Cross-Match

D. Cucchiari¹, V. Tubita², M. J. Ramirez-Bajo², J. Rovira², F. E. Borràs³, L. Carreras-Planella³, A. Hertig⁴, F. Oppenheimer¹, F. Diekmann¹, I. Revuelta¹

¹Renal Transplant Unit, Hospital Clínic, Barcelona, Spain, ²Laboratori Experimental de Nefrologia i Trasplantament, IDIBAPS, Barcelona, Spain, ³REMAR-IVECAT group, IGTP, Badalona, Spain, ⁴Department of Nephrology and Kidney Transplantation, Hôpital Tenon, Paris, France

Meeting: 2019 American Transplant Congress

Abstract number: A135

Keywords: B cells, FACS analysis, Highly-sensitized, Rejection

Session Information

Session Name: Poster Session A: Biomarkers, Immune Monitoring and Outcomes

Session Type: Poster Session

Date: Saturday, June 1, 2019

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

*Purpose: Kidney transplant recipients undergoing desensitization for a positive cross-match are at very high risk of developing Antibody-Mediated Rejection (AMR). Because of desensitization, peripheral circulating B cells and donor-specific antibodies are of little value as biomarkers. We hypothesized that B-cell derived exosomes may reveal the proliferation of tissue-resident B cells that would not be otherwise detectable in peripheral blood. This would constitute an earlier biomarker of AMR in this very delicate cohort of patients.

*Methods: we studied 11 cross-match positive patients desensitized with rituximab, plasma exchange and immunoglobulins (DS group). Control groups were cross-match negative patients, 10 hypersensitized (cPRA>85%, HS group) and 9 with low immunological risk (cPRA<10%, CT group). Enriched pools of exosomes were isolated through size-exclusion chromatography from stored serum samples and studied for CD19 and HLA-II expression as markers of B cells origin by beads-based flow cytometry. MFI values were normalized with the exosomal biomarker CD9. All groups were analyzed at three time points: T1) pre-transplant T2) first biopsy (either for rejection or for protocol) and T3) 1 year. In the DS group, another time point was before starting desensitization.

*Results: In the DS group, CD19- and HLA-II-positive exosomes dropped after desensitization (P<0.01) and were lower compared with the HS group at T1 (P=0.06 for CD9) and at T2 (P=0.04 for CD19 and P=0.03 for HLA-II). Within the DS group patients who developed AMR (7 patients at T2 and 5 patients at T3) had significantly higher expression of CD19- and HLA-II-positive exosomes compared to those who did not reject (P=0.03 and P=0.02 for CD19 at T2 and T3 and P=0.01 and P<0.01 for HLA-II at T2 and T3, respectively).

*Conclusions: B-cell derived exosomes dropped significantly after desensitization in comparison with a paired-risk group. However, those patients who later developed AMR experienced a significant relapse in CD19- and HLA-II-positive exosomes. This may reflect residual or rebound of B cell activity after desensitization and could be used as an early biomarker of AMR in this cohort.

To cite this abstract in AMA style:

Cucchiari D, Tubita V, Ramirez-Bajo MJ, Rovira J, Borràs FE, Carreras-Planella L, Hertig A, Oppenheimer F, Diekmann F, Revuelta I. B Cell Derived Exosomes Are Associated with Antibody Mediated Rejection in Kidney Transplant Recipients Desensitized for a Positive Cross-Match [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/b-cell-derived-exosomes-are-associated-with-antibody-mediated-rejection-in-kidney-transplant-recipients-desensitized-for-a-positive-cross-match/. Accessed November 22, 2024.

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