Efficacy of Intravenous Immunoglobulin in Eliminating De Novo Donor-Specific Antibodies After Lung Transplantation: Importance of Early Intervention

The development of de novo donor-specific anti-HLA antibodies (dnDSA) after lung transplantation (LuTX) has been increasingly linked to the onset of antibody-mediated rejection (AMR), chronic lung allograft dysfunction (CLAD), and impaired long-term outcomes. However, the therapeutic impact of intravenous immunoglobulin (IVIG) therapy in patients with dnDSA remains unclear. We conducted a retrospective single-center study of LuTX recipients (2015-2019) who developed dnDSA post-transplantation and received IVIG-based therapy. Patients were classified as responders or non-responders based on post-treatment antibody clearance. Clinical, immunological and functional outcomes were compared. Among 47 patients with dnDSA and IVIG-based therapy, 23 (48.9%) achieved complete antibody elimination. Preemptive treatment, defined as initiation of IVIG therapy before onset of clinical symptoms, was found to be an independent predictor of antibody clearance (odds ratio 29.5; p = 0.013). Responders showed significantly lower baseline MFI. While differences in CLAD-free survival favored responders, they did not reach statistical significance. Preemptive IVIG therapy in asymptomatic dnDSA-positive LuTX recipients may enhance antibody clearance and reduce CLAD risk. These findings support early intervention strategies and underscore the need for prospective trials to define optimal therapeutic thresholds and timing.