Preemptive treatment of early donor-specific antibodies with IgA- and IgM-enriched intravenous human immunoglobulins in lung transplantation

Abstract

This retrospective study presents our 4-year experience of preemptive treatment of early anti-HLA donor specific antibodies with IgA- and IgM-enriched immunoglobulins. We compared outcomes between patients with antibodies and treatment (case patients) and patients without antibodies (control patients). Records of patients transplanted at our institution between March 2013 and November 2017 were reviewed. The treatment protocol included one single 2 g/kg immunoglobulin infusion followed by successive 0.5 g/kg infusions for a maximum of 6 months, usually combined with a single dose of anti-CD20 antibody and, in case of clinical rejection or positive crossmatch, with plasmapheresis or immunoabsorption. Among the 598 transplanted patients, 128 (21%) patients formed the case group and 452 (76%) the control group. In 116 (91%) patients who completed treatment, 106 (91%) showed no antibodies at treatment end. Fourteen (13%) patients showed antibody recurrence thereafter. In case versus control patients and at 4-year follow-up, respectively, graft survival (%) was 79 versus 81 (P = .59), freedom (%) from biopsy-confirmed rejection 57 versus 53 (P = .34), and from chronic lung allograft dysfunction 82 versus 78 (P = .83). After lung transplantation, patients with early donor-specific antibodies and treated with IgA- and IgM-enriched immunoglobulins had 4-year graft survival similar to patients without antibodies and showed high antibody clearance.

Six‐year experience with treatment of early donor‐specific anti‐HLA antibodies in pediatric lung transplantation using a human immunoglobulin‐based protocol

“…eDSA clearance was defined as the absence of DSA in two consecutive Luminex‐based SPA controls (LIFECODES; Immucor Transplant Diagnostics, Inc, Stamford, CT) after treatment initiation. DSA recurrence was defined as a renewed positivity of previously cleared DSA …”

“…Contrarily to adult lung‐transplanted patients, a surveillance protocol with transbronchial biopsies at 1, 3, and 6 months and 1 year after pediatric lung transplantation has only recently been introduced at our institution. Before 2018, only older children (>11 years old) underwent transbronchial biopsies, usually upon indication.…”

“…In the Luminex analysis, a threshold of 1000 median fluorescence intensity (MFI) was used to detect eDSA. In eDSA + /IVIG + patients, Luminex‐based DSA controls were additionally performed immediately before each IVIG treatment session and every 6 months after treatment end …”

“…The detection of early anti‐HLA donor‐specific antibodies (eDSA) after lung transplantation has been associated with poorer graft survival, antibody‐mediated rejection (AMR), and later development of chronic lung allograft dysfunction (CLAD) . Protocols have been developed to treat eDSA and suspected AMR, but the available case series are limited to nonrandomized, usually retrospective, studies . At our Institution, since 2013, a protocol based on successive infusions of intravenous human immunoglobulins (IVIG) has shown good eDSA clearance rates and similar outcomes in patients with vs without eDSA …”

“…Protocols have been developed to treat eDSA and suspected AMR, but the available case series are limited to nonrandomized, usually retrospective, studies . At our Institution, since 2013, a protocol based on successive infusions of intravenous human immunoglobulins (IVIG) has shown good eDSA clearance rates and similar outcomes in patients with vs without eDSA …”