Elevated pretransplantation soluble BAFF is associated with an increased risk of acute antibody-mediated rejection

Abstract

Background: B cells play an important role in renal allograft pathology, particularly in acute and chronic antibody-mediated rejection (AMR). B-cell activating factor belonging to the tumor necrosis factor family (BAFF; also known as BLyS) is a cytokine that enhances B-cell survival and proliferation.

Methods: We analyzed serum BAFF levels in 32 patients undergoing antibody-incompatible (Ai) renal transplantation and 319 antibody-compatible transplant recipients and sought to determine whether there was a correlation with acute rejection and with transplant function and survival.

Results: We demonstrate that, in patients undergoing Ai transplantation, elevated serum BAFF levels at baseline (before both antibody removal/desensitization and transplantation) are associated with an increased risk of subsequent AMR. In antibody-compatible transplant recipients at lower risk of AMR, no statistically significant association was observed between pretransplantation serum BAFF and AMR.

Conclusions: These data raise the possibility that, in high immunologic risk patients undergoing Ai transplantation, the presence of elevated pretransplantation serum BAFF might identify those at increased risk of AMR. BAFF neutralization may be an interesting therapeutic strategy to explore in these patients, particularly because such agents are available and have already been used in the treatment of autoimmunity.

Figures

FIGURE 1

Elevated pretransplantation serum BAFF in Ai transplant recipients. A, baseline serum BAFF levels (predesensitization and pretransplantation) in Ai transplant recipients ranged from 0 to 2200 ng/mL, with a trend toward a higher median value in those who experienced AMR. B, patients within the highest serum BAFF tertile had an increased frequency of AMR and reduced rejection-free survival. C, P=0.01 based on a chi-square test for trend indicating an association between increasing BAFF levels and rejection. D and E, there was no association between pretransplantation BAFF levels and DSA titre (mfi, median fluorescence intensity). F, total lymphocyte count and serum BAFF. Horizontal bars represent median values. Shaded area in F indicates laboratory normal range. P values calculated using Mann–Whitney (A), log-rank (Mantel–Cox; C) and Kruskal–Wallis (D and E) tests, and linear regression analysis (F).

FIGURE 2

Pretransplantation serum BAFF in Ac transplant recipients. A, baseline serum BAFF ranged from 0 to 539 ng/mL (horizontal lines represent median values). B, a higher proportion of patients with a pretransplantation BAFF level more than 100 ng/mL experienced an episode of AMR compared with those with a pretransplantation BAFF level less than 100 ng/mL, but this did not reach statistical significance. There was no association between pretransplantation BAFF levels and subsequent T-cell–mediated acute rejection (C), pretransplantation total lymphocyte count (D), or pretransplantation sensitization status (E). P values calculated using Mann–Whitney (A), chi-square test for trend (B, C, and E), and linear regression analysis (D).

FIGURE 3

Pretransplantation serum BAFFand long-term allograft outcomes. Elevated pretransplantation serum BAFF was not associated with an increase in serum creatinine at 1 and 2 years after transplantation in either cohort 1 (Ai; A) or cohort 2 (Ac; B). GL, grafts lost (Cr recorded as 500 μL/mL); N, number included; n/a, follow-up time not reached; PD, patient deaths; UK, number with creatinine unknown. Pretransplantation BAFF did not significantly influence allograft survival in either cohort 1 (C) or cohort 2 (D). P values calculated using Kruskal–Wallis (A and B) and log-rank (Mantel–Cox; C and D) tests.