*Purpose: Antibody-mediated rejection (AMR) after lung transplant (LT) is a serious complication, potentially leading to graft failure despite advances in drug therapy. Diagnosis and treatment of AMR remains challenging, especially as it pertains to the role of donor specific antibodies (DSA). The purpose of this study was to determine the effect of DSA development on clinical outcomes.

*Methods: This retrospective, single center study, included patients that received a LT between Jan 2015 and Mar 2019. Pulmonary function test (PFT) results were collected along with DSA development (and specificities), biopsy results, survival, and AMR treatment modalities. DSAs were measured with LABScreen® Single Antigen Class I and II beads with a mean fluorescent intensity cutoff of 3000. The primary outcome was the incidence of significant lung dysfunction in patients who developed DSA vs those who did not. A decrease in forced expiratory volume in one second (FEV1) of at least 10% from baseline to end of study period was considered significant. Secondary outcomes included the effect of AMR treatment on lung function, the incidence and time to development of DSA, and the effects of specific DSA on severity of lung dysfunction.

*Results: Ninety patients were included in the analysis with a mean follow-up period of 21 months (±15.8). Over the course of the study, 24 patients (27%) developed DSA. The median time to formation of DSA was 210 days post-transplant (IQR 57 to 449). The observed survival at 1 year and 3 years in DSA-positive patients was 92% and 83% respectively compared to 85% and 82% in non-DSA patients. Of the 24 patients that developed DSAs, 15 received treatment, most commonly with intravenous immunoglobulin with plasmapheresis (53%). Rate of significant lung dysfunction was 47% in the DSA group (n=21) vs 33% in the DSA negative group (n=59) (p=0.3). The median decline in FEV1 for DSA-positive patients who received treatment (n=12) was 16% compared to 7.2% for those who did not (n=9) (p=0.095). DSA positive patients were grouped into those with HLA-DQ versus all other HLA. Median decline in FEV1 from baseline in HLA-DQ was 10.7% compared to HLA-other 3.5% (p=0.095). Four patients had HLA-DQ in combination with other HLA; comparison of the percentage change in FEV1 in these patients to HLA-DQ alone, 27% vs 10.7% also indicated no significant difference (p=0.095).

*Conclusions: Concluding, we observed numerically greater but not statistically significant decreases in lung function in DSA positive patients and those who were positive for HLA-DQ. Nevertheless, the high prevalence of HLA-DQ in patients exhibiting greater decline in lung function suggests it may be an indicator of AMR that merits further investigation.

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