*Purpose: De novo donor-specific antibodies (DSA) are a risk factor for antibody mediated rejection (AMR) and poor clinical outcomes after lung transplant (LT). Intravenous immune globulin (IVIG) neutralizes circulating DSA and is thought to disrupt AMR. We tested the hypothesis that IVIG therapy is associated with reduced DSA intensity and increased FEV1 compared to observation alone.

*Methods: LT recipients from 2009 to 2019 with de novo DSA with mean fluorescence intensity (MFI) >3000 were included in this retrospective, single-center, observational analysis. Subjects were excluded if they had treatment in addition to IVIG, had a positive crossmatch, had IVIG prior to DSA, or had no follow-up DSA in 28-100 days. Subjects received IVIG only (n=23) or did not receive treatment (n=16). The trajectories of DSA MFI and FEV1 between the index and follow-up DSA were each tested via repeated measures analysis of variance with time by treatment group interaction effects. Additional outcomes were chronic lung allograft dysfunction and survival. Between-group comparisons were made using parametric and non-parametric tests and Kaplan Meier survival methods.

*Results: The study cohort included 39 LT patients (mean age 53±13y, 59% male, 80% double LT) with most having IPF (41%) or COPD (36%). The majority (85%) of DSAs targeted class II antigens. These baseline characteristics and the median interval between index and follow-up testing did not differ between groups (all p>0.203). While overall DSA MFI decreased over time (p=0.003), there was no significant difference in the trajectory of MFI between treatment groups (Panel A, p=0.789). In contrast, the trajectory of FEV1 increased over time in the IVIG group, but not in the no treatment group (Panel B, time by treatment interaction p=0.003). Mean FEV1 at DSA detection was 2.04±0.72 and 2.49±0.77 for the IVIG and no treatment groups, respectively (p=0.087). There was no between-group difference in CLAD (22% vs. 38%, p=0.307) or patient survival (log rank p=0.396).

*Conclusions: Although patients treated with IVIG alone for de novo DSA after LT have similar DSA MFI trajectories over time, their FEV1 increased after therapy. This result may be due to the trend towards lower FEV1 in the IVIG group at the time of DSA detection. Future studies are needed to determine the mechanisms by which IVIG affects FEV1 in the setting of DSA.

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