Renal Transplant Status Correlates With Expression of BAFF and Localises Within Intra-Graft Lymphoid Aggregates During Acute Antibody-Mediated Rejection.

Abstract

Purpose of Study: To measure serum and intra-renal expression of B cell-activating factor (BAFF) as a marker of B cell-mediated pathology. Methods: CD19+ cells from patients with deteriorating (n=33), stably-impaired (n=29) and stable (n=31) grafts were examined for CD19, CD27, IgD & BAFF-receptor (BAFF-R) expression by flow cytometry. Serum BAFF (sBAFF) levels were measured by ELISA and HLA antibodies using Luminex technology. Renal biopsy sections from cohorts with (n=16) and without (n=11) acute antibody-mediated rejection (AAMR) were studied by immunohistochemistry. Results: The stable group had significantly lower sBAFF and more CD19+BAFF-R+cells. Those with above average sBAFF (sBAFFhigh) had a higher rate of allograft deterioration and greater prevalence of donor-specific HLA antibody compared to those with below average sBAFF levels. Moreover, naïve B cells (CD19+CD27-IgD+) were reduced and memory B cells (CD19+CD27+IgD-) increased in sBAFFhigh patients. Examination of biopsy sections demonstrated a higher frequency of CD19+ cells associated with small populations of sub-capsular interstitial lymphoid aggregates in patients with AAMR. BAFF-R expression showed a similar distribution to CD19, but BAFF more often had a diffuse distribution across the core. The presence or absence of AAMR made no difference to sBAFF levels. Conclusion: BAFF is a central component of the B cell compartment regulating cell maturation and survival. Here elevated expression of sBAFF and low frequency of BAFF-R on CD19 cells correlate with deteriorating graft function and intra-renal expression of CD19, BAFF-R and BAFF is increased during AAMR. These data provide direct evidence of BAFF expression on infiltrating B cells during humoral rejection, and a rationale for measuring expression levels of BAFF as a biomarker of allograft function.