Non-HLA Antibodies and the Risk of Antibody-mediated Rejection without Donor-specific Anti-HLA Antibodies After Lung Transplantation

Background

Antibody-mediated rejection (ABMR) has become one of the leading causes of chronic lung graft dysfunction. However, in lung transplantation, this entity is sometimes difficult and controversial to diagnose. It is mainly caused by the appearance of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA), although there are situations with C4d deposits in biopsy in the absence of circulating DSA. The aim of this work was to study the potential role of non-HLA antibodies in the development of ABMR without DSA after lung transplantation.

Methods

A case-control study was designed with a cohort of lung transplant recipients at our institution. Twenty-seven patients with ABMR and without anti-HLA antibodies were identified after lung transplantation, and a control group of 21 transplant recipients was selected with the same post-transplant follow-up without evidence of rejection. Non-HLA antibodies were studied pretransplant using Luminex (ThermoFisher, One Lambda).

Results

The median of the pretransplant non-HLA–positive antibodies in the group with ABMR without DSA is significantly higher than in the control group: 2 (interquartile range, 0–16) vs 0 (interquartile range, 0–1; P < .01). Patients with >1.5 pretransplant non-HLA antibodies were more likely to develop ABMR without DSA (sensitivity, 80.95%; specificity, 55.55%; area under the curve, 71.3%).

Conclusion

The increase of non-HLA antibodies before lung transplantation has recently been shown to increase the risk of chronic lung allograft dysfunction. These results confirm that patients with a higher number of non-HLA antibodies could be at risk of developing ABMR without DSA. These results point out the possible usefulness of pre-lung transplant non-HLA antibodies to identify patients with end-stage lung disease at risk of developing ABMR without DSA.