Introduction: In last years, antibody-mediated rejection (AbMR) has been identified as the leading cause of death-censored graft loss of kidney transplants. Despite the growing recognition of the role of the B-lymphocyte subpopulation in the development of both tolerance and rejection, little is known about the trigger mechanisms and effectors of this humoral response. The B-cell activating factor BAFF contributes to the development and maturation of B-lymphocytes, but current data about its role in the generation of donor-specific antibodies (DSA) and in the subsequent appearance of AbMR are inconsistent.
Materials and Methods: We performed a prospective study including both indication and one-year protocol kidney transplant biopsies carried out in our center between January/2015 and February/2017. Serum samples were collected at the day of the graft biopsy and one month later and soluble BAFF levels were measured by ELISA.
Results and Discussion: 60 biopsies were performed at a median time of 1.11 year (IQR 098, 1.99 years). Median soluble BAFF levels were 445 pg/ml (IQR 318, 630). AbMR was diagnosed in 30 biopsies. Area under the ROC curve of soluble BAFF for predicting AbMR was 0.661 (95%CI 0.521-0.800, p = 0.033). Mean values of soluble BAFF were significantly higher in patients with AbMR (588 ± 312 pg/ml vs. 416 ± 177 pg/ml, p = 0.033). Mean values of soluble BAFF were significantly higher in patients with DSA (605 ± 259 pg/ml vs. 428 ± 249 pg/ml, p = 0.005). BAFF levels related to Banff scores g (r = 0.376, p = 0.003) and cg (r = 0.351, p = 0.007) and to albuminuria (r = 0.403, p = 0.003). One-month post-biopsy serum BAFF levels were lower in 6 patients who receive IVIG therapy but without reaching statistically significant differences (-87 ± 139 pg/ml vs. 40 ± 127 pg/ml, p = 0.062).
Conclusion: Serum soluble BAFF levels show a moderate ability to predict the diagnosis of AbMR in a kidney graft biopsy. Higher BAFF levels in patients with DSA and AbMR suggest that BAFF contributes to the pathogenesis of antibody-mediated graft damage. BAFF related graft injury is more prominent in the glomerular compartment. IVIG mechanism of action in AbMR therapy can be partly mediated through BAFF reduction.