Following kidney transplantation, rejection and the presence of interstitial fibrosis and tubular atrophy represent prognostically unfavorable factors and are associated with reduced graft survival. The B-cell activating factor (BAFF) and the profibrotic glycoprotein Dickkopf 3 (DKK3) have been suggested as potential biomarkers and therapeutic targets.
In our rat model, we hypothesized that anti-BAFF treatment could not only influence cellular migration patterns but also mediate intragraft fibrosis and modulate DKK3 expression.
In an allogeneic setting, kidneys of Brown Norway rats were transplanted into Lewis rats with cyclosporine A (CyA) as standard immunosuppressive therapy (highCNI). To permit chronic rejection and the development of donor-specific antibodies (DSA), some rats received a reduced dosage of cyclosporine A (lowCNI), while another group additionally received a monoclonal anti-BAFF antibody (lowCNI+anti-BAFF) to mitigate immunological activation.
The highCNI group exhibited the least immune cell infiltration (CD3/20/68) and lower fibrosis, despite a tendency toward higher DKK3 mRNA levels on day 28. The lowCNI group showed the highest cellular infiltration, accompanied by the most severe fibrosis and a trend toward increased DKK3 expression. In contrast, the lowCNI+anti-BAFF group demonstrated reduced B-cell infiltration, mild fibrosis, and low DKK3 expression.
Thus, the results indicate that the addition of anti-BAFF treatment, can eliminate the detrimental effects of under- and over-immunosuppression.