Distinct Clinical Relevance of BAFF Expression Within the Kidney Graft and Soluble BAFF Serum Levels Indicate Confined Alloimmune Responses Disconnected from the Periphery

E. Campos,^1,2 K. Mine,¹ A. Goncalves-Primo,^1,2 M. Soares,⁴ M. Franco,² J. Medina-Pestana,^2,3 H. Tedesco-Silva,³ M. Gerbase-DeLima.^1,2

¹Instituto de Imunogenética, AFIP, São Paulo, SP, Brazil
²Universidade Federal de São Paulo, São Paulo, SP, Brazil
³Hospital do Rim e Hipertensão- FOR, São Paulo, SP, Brazil
⁴Universidade Federal do Parana, Curitiba, PR, Brazil.

Meeting: 2015 American Transplant Congress

Abstract number: C243

Keywords: B cells, Gene expression, HLA antibodies, Outcome

Session Information

Session Name: Poster Session C: Translational Biomarkers and Immune Monitoring

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

As soluble B-cell activating factor (BAFF) serum levels (sBAFF) may not reflect BAFF concentrations within the graft, what could be related to the inconsistencies in studies exploring them as markers of humoral immunity in kidney transplantation (K-Tx), we investigated to what extent sBAFF reflected intragraft BAFF transcripts (tBAFF), and explored correlations of sBAFF and tBAFF with circulating B cells phenotypes and K-Tx outcomes. Methods: sBAFF (ELISA) and relative expression (real time PCR) of the gene coding BAFF, along with other genes involved in humoral immunity, within the graft, were evaluated in 129 K-Tx recipients (R). Donor specific HLA antibodies (DSA) were determined by Luminex single antigen assay. Graft lesions were classified (Banff 2007) by two pathologists and total-i (ti) score was also determined. Circulating B cells were phenotyped by flow cytometry in 79 R. Estimated (MDRD) glomerular filtration rate (eGFR) was used to assess graft function. Results: sBAFF weakly correlated to tBAFF (p<0.001; r=0.36); tBAFF, but not sBAFF, levels were higher in R with: DSA (pan-IgG) >5000 MFI (p=0.002) and with DSA positive in the C1q Luminex test (p=0.07), with cellular (p=0.05) and humoral (p=0.06) rejection, and with ti score ≥ 1 (p<0.001). Only sBAFF correlated with frequencies of memory (p=0.04, r=-0.23) and naïve (p=0.02 r=0.26) B cells. R receiving micophenolic acid presented less memory (p=0.004) and more naïve (p=0.004) B cells, as well as higher sBAFF (p<0.001) and tBAFF (p=0.02), as compared to R receiving azathioprine. Only tBAFF correlated with expression of genes coding for molecules involved in lymphoid neogenesis (CCL21: p<0.001, r=0.57; CXCL13: p<0.001, r=0.44) and plasma cell survival (APRIL: p=0.002, r=0.28) within the graft. Only tBAFF associated (RR: 3.7) with eGFR ≤ 30 mL/min at the end of 25.2 months of follow-up after biopsy. In conclusion, the impact of graft tBAFF is not reproduced in serum sBAFF, what could indicate local alloimmune responses disconnected from the periphery.

To cite this abstract in AMA style:

Campos E, Mine K, Goncalves-Primo A, Soares M, Franco M, Medina-Pestana J, Tedesco-Silva H, Gerbase-DeLima M. Distinct Clinical Relevance of BAFF Expression Within the Kidney Graft and Soluble BAFF Serum Levels Indicate Confined Alloimmune Responses Disconnected from the Periphery [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/distinct-clinical-relevance-of-baff-expression-within-the-kidney-graft-and-soluble-baff-serum-levels-indicate-confined-alloimmune-responses-disconnected-from-the-periphery/. Accessed November 21, 2024.

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