Seven-Year Clinical Results of an IgA-and IgM-Enriched Human Immunoglobulin-Based Therapy for Antibody-Mediated Rejection after Lung Transplantation

Purpose Development of anti-HLA donor specific antibodies early after lung transplantation (eDSA) has been associated with antibody-mediated rejection (AMR) and poor graft survival. Since 2013, our institution has employed successive infusions of IgA- and IgM-enriched intravenous immunoglobulins (IgGAM, first infusion: 2gr/kg, then 0.5gr/kg once every 4 weeks for a maximum of 6 months) as 1st line treatment in such cases. Asymptomatic eDSA development (possible subclinical AMR) was treated with IgGAM only. Patients with concomitant graft dysfunction (possible clinical AMR) or positive crossmatch additionally receive 5 sessions of plasmapheresis pre-IgGAM, and a single dose of anti-CD20 antibody (Rituximab) afterwards. This study was presents 7-year results of this IgGAM-based protocol. Methods Records of patients transplanted between 02/2013 and 10/2020 were reviewed. Outcomes were compared between patients with eDSA and treated with IgGAM (IgGAM group) and those without eDSA (control group). Median follow-up was 41 (18-64) months. Results he 913 transplanted recipients, 224 (25%) patients were included in the IgGAM group and 667 (73%) the control group. The remaining 22 (2%) patients (13 patients with eDSA but not treated, and 9 patients treated only with tPE and Rituximab) were excluded. Forty-one (18%) IgGAM patients exhibited pre-formed eDSA and 16 (7%) patients showed a positive retrospective crossmatch. Thirty-six (16%) patients showed concomitant graft dysfunction (possible clinical AMR). Median time to eDSA detection was 14 days post-transplant. At follow-up end, treatment was completed in 204 (91%) patients (ongoing treatment, n=7; in-hospital deaths, n=4; treatment prematurely interrupted, n=9). In these 204 patients, IgGAM treatment cleared eDSA in 184 (90%) patients. Twenty-five (12%) patients developed eDSA recurrence at a median of 9 months after completing treatment. Clearance was less effective in patients with preformed eDSA (p Conclusion In lung recipients, treatment of eDSA with IgGAM yielded high eDSA clearance. Patients with eDSA and IgGAM-treatment have good 7-year graft survival similar to control patients.