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

Background: The development of anti-HLA donor-specific antibodies early after lung transplantation (eDSA) has been associated with antibody-mediated rejection (AMR) and poor graft survival. At our institution, since 2013, successive infusions of IgA- and IgM-enriched human intravenous immunoglobulins (IgGAM, first infusion: 2 gr/kg, then 0.5 g/kg once every 4 weeks for a maximum of 6 months) formed the backbone of eDSA therapy. Actually, patients with only evidence of eDSA (possible subclinical AMR) are treated with IgGAM only. Patients with concomitant graft dysfunction (possible clinical AMR) or preformed DSA (positive virtual crossmatch) receive additionally plasmapheresis (PE) or immunoabsorption before the first IgGAM dose, and a single dose of anti-CD20 antibody (Rituximab) thereafter. Aims of this study were to present the 7-year results of the IgGAM-based therapy.

Method: Records of patients transplanted at our institution between 02/2013 and 08/2021 were reviewed. Outcomes were compared between patients with eDSA and treated with IgGAM (IgGAM group) and without eDSA (control group). Median (IQR) follow-up was 45 (21–71) months.

Results: During the study period, among the 987 transplanted patients, 246 (25%) patients formed the IgGAM group and 718 (73%) the control group. The remaining 23 (2%) patients (14 patients with eDSA but not treated, and 9 patients treated only with tPE and Rituximab) were excluded.

Forty-nine IgGAM patients (20%) showed pre-formed eDSA and 39 (16%) patients concomitant graft dysfunction. Median time to eDSA detection was 14 days after transplantation. At follow-up end, treatment was completed in 226 (92%) patients (still on treatment, n = 7; in-hospital deaths, n = 4; treatment interrupted earlier as intended by protocol, n = 9). In these patients, IgGAM treatment cleared eDSA in 205 (91%) patients, 28 (14%) patients showing eDSA recurrence a median of 9 months after treatment end. Clearance was worse in patients with preformed eDSA (p < 0.001).

In IgGAM versus control patients and at 8-year follow-up, respectively, graft survival (%) was 67 versus 68 (p = 0.65) and freedom from CLAD 64 versus 62 (p = 0.83). Graft and CLAD-free survival did not differ between IgGAM patients with and without graft dysfunction.

Conclusion: After lung transplantation, a treatment protocol for eDSA based on IgGAM yielded high eDSA clearance. Patients with eDSA and IgGAM treatment have good 8-year graft survival similar to control patients.

Publication History

Article published online:
03 February 2022