Non-Human Leukocyte Antigen Antibody-Mediated Lung Transplant Rejection: The Other Anti-A

Background: Acute rejection of lung allografts is an important contributor to morbidity and mortality in the transplant patient population, resulting in the dysfunction and destruction of the graft by the host's immune system via cellular or antibody-mediated mechanisms. Acute cellular rejection (ACR) is more common and better characterized than antibody-mediated rejection, which to date lacks any widely agreed upon, standardized set of diagnostic criteria. We present a case of AMR attributable to a rare phenomenon, non-human leukocyte antigen (HLA) antibodies.

Case Report: A 50-year-old male underwent an uneventful single lung transplant for pulmonary sarcoidosis. Donor and recipient blood type was A positive. No pretransplant donor-specific antibodies were identified. Flow cytometric crossmatch was negative. The postoperative course was significant for a single-unit transfusion of packed red blood cells on postoperative day (POD) 1 and persistent asymptomatic Serratia marcescens in bronchial washes despite ongoing levofloxacin treatment. A surveillance biopsy (POD 34) showed no evidence of rejection. One week later (on POD 41), the patient presented with fever, shortness of breath, and imaging abnormalities of the grafted lung. Inpatient antibiotic escalation to cefepime, ertapenem, and meropenem resolved the positive cultures and fever, but the patient's respiratory function continued to decline, requiring intubation and extracorporeal membrane oxygenation. High-dose steroids and therapeutic plasma exchanges were initiated for suspected acute rejection. During the workup, a newly developed anti-A1 red blood cell antibody was identified. Despite supportive efforts, the patient died on POD 55, 14 days after symptomatic presentation.

Conclusion: This case highlights the clinical significance of AMR in lung allografts, as well as the need to investigate both HLA and non-HLA antibody sources in pulmonary transplant rejection refractory to treatment.