Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients

Abstract

It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05). Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes.

High Pretransplant BAFF Levels and B-cell Subset Polarized towards a Memory Phenotype as Predictive Biomarkers for Antibody-Mediated Rejection

“…We also observed that serum BAFF levels, measured at 6 and at 12 months after transplantation were also higher in those patients with subclinical antibody-mediated rejection detected in the surveillance biopsy, corroborating the possible contribution of BAFF to the pathogenesis of antibody-mediated graft damage. Considering this aspect, Won Min et al described that while pretransplant BAFF levels showed significant association with early rejection, posttransplant BAFF levels measured at the time of indication biopsy are not associated with allograft rejection [25].It is important to highlight some relevant aspects of our study such as the prospective monitoring of the kidney transplant patients at 6 and at 12 months after kidney transplantation, which differentiates it from other transversal studies or with a shorter period of follow-up [28,29]. In the same way we would like to emphasize the importance of surveillance biopsy that gives up data about the possible existence of a subclinical rejection.…”

“…However, in the context of transplantation, there are less studies and the role of BAFF is more controversial. On the one hand, some authors indicate that BAFF reflects the immunological risk profile of patients after kidney transplantation (KT), considering that pretransplant BAFF levels are associated with pretransplant sensitization and are useful in predicting allograft rejection [23][24][25]; BAFF expression correlates with pretransplant panel reactive antibody (PRA), indicating that BAFF may be involved in the development of graft loss [26]; elevated levels of BAFF are associated with antibody-mediated clinical damage in KT [27], and with an increased risk of acute AbMR [28][29][30]. On the other hand, there are authors that affirm that BAFF is not a prognostic marker for allograft dysfunction or survival in KT patients because BAFF serum levels are not related to anti-HLA sensitization [31]; significantly lower levels of BAFF are found in patients experiencing AbMR [32]; or high BAFF is not associated with the graft outcome in KT with rituximab induction [33].…”

B-Cell-Activating Factor and the B-Cell Compartment in HIV/SIV Infection

“…Elevated circulating levels of BAFF and/or APRIL are associated with autoimmune diseases, chronic inflammation ( 14 , 88 ), or occur after CD20 B-cell depleting therapy ( 89 , 90 ). Because chronic inflammation and hypergammaglobulinemia are hallmarks of chronic HIV-1 infection, serum BAFF levels were first measured in chronically HIV-infected individuals ( 91 ).…”

Böbrek Naklinde Kullanılan Yeni İmmünsupresif İlaçlar

“…Nakil öncesi BAFF seviyelerinin nakil sonrası de novo anti-HLA antikor gelişimi ve antikor aracılı rejeksiyon ile ilişkili olduğu bilinmektedir. Posttransplant endikasyon biyopsilerindeki BAFF seviyelerinin ise de novo HLA-DSA gelişimi, biyopsi bulguları veya allograft rejeksiyonu ile ilişkili olduğu gösterilememiştir (47). Renal transplant hastalarında, BAFF seviyeleri ile HLA I ve HLA II antikorları arasında pozitif korelasyon saptanmıştır.…”