Alin Girnita

Proteasome inhibitor therapy for antibody-mediated rejection

Woodle ES, Walsh RC, Alloway RR, Girnita A, Brailey P. Proteasome inhibitor therapy for antibody‐mediated rejection.
Pediatr Transplantation 2011: 15: 548–556.

IGG3 anti-HLA donor-specific antibodies and graft function in pediatric kidney transplant recipients

Anti‐HLA DSAs are associated with ABMR and graft loss in KT recipients, yet the influence of DSA IgG subclass on outcomes in pediatric KT recipients is not completely understood. We performed a single‐center retrospective chart review of pediatric KT recipients with anti‐HLA DSAs, aiming to study the association between specific DSA IgG subclasses and graft outcomes, including ABMR and significant graft dysfunction (graft loss or 50% decrease in eGFR). Thirty‐six patients (mean age 15.4y) with DSAs initially detected 1 month‐14.3 years post‐transplantation were followed for a median of 2.8 years. Rates of IgG1, 2, 3, and 4 subclass detection were 92%, 33%, 58%, and 25%, respectively. Twenty‐two patients (61%) had clinical ABMR, whereas 19% had subclinical ABMR, and 13 (36%) experienced significant graft dysfunction. Patients with IgG3+ DSAs had a higher risk of graft dysfunction compared with IgG3‐ patients (52% vs 13%, P = .03). In a multiple Cox proportional regression analysis, the presence of IgG3+ DSA was independently associated with significant graft dysfunction (HR 10.45, 95% CI 1.97‐55.55, P = .006). In conclusion, IgG3 subclass DSAs are associated with graft dysfunction and may be useful for risk stratification and treatment decisions in DSA‐positive pediatric KT recipients.