Intravenous Immunoglobulins Alone for the Desensitization of Lung Transplant Recipients with Preformed Donor Specific Antibodies and Negative Flow Cytometry Crossmatch

Clin Transplant. 2024 Jul;38(7):e15374. doi: 10.1111/ctr.15374.

Abstract

Background: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach.

Methods: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models.

Results: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups.

Conclusion: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.

Keywords: antibody‐mediated rejection; anti‐HLA antibodies; immunoglobulin; lung transplantation.

MeSH terms

  • Adult
  • Desensitization, Immunologic* / methods
  • Female
  • Flow Cytometry*
  • Follow-Up Studies
  • Graft Rejection* / etiology
  • Graft Rejection* / immunology
  • Graft Survival* / immunology
  • HLA Antigens* / immunology
  • Histocompatibility Testing
  • Humans
  • Immunoglobulins, Intravenous* / administration & dosage
  • Immunoglobulins, Intravenous* / therapeutic use
  • Immunologic Factors / therapeutic use
  • Isoantibodies* / blood
  • Isoantibodies* / immunology
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Tissue Donors*
  • Transplant Recipients

Substances

  • Immunoglobulins, Intravenous
  • Isoantibodies
  • HLA Antigens
  • Immunologic Factors