Antibody-mediated rejection after lung transplantation (LTX) with and without donor specific antibodies?

Donor specific anti-HLA antibodies (DSA) are considered to be risk factors for the development of antibody-mediated rejection (AMR) after LuTX. However, diagnostic and treatment still are not standardized.

Case 1:

DSA (18.600MFI) were detected after LuTX. The patient developed respiratory insufficiency and pericardial and loculated pleural effusions in CT scan three weeks after LuTX. CRP increased to 12,6 mg/dl without signs of infection in the bronchoscopy and BAL. Acute cellular rejection was suspected and corticosteroid-pulse therapy was performed. Antibiotic therapy was escalated due to further increasing of CRP (40 mg/dl) but without benefits. With the suspicion of AMR (without histological signs) the patient was treated with plasmapheresis and IgM-enriched immunoglobulins with complete clinical improvement within two weeks.

Case 2:

Five weeks after LuTX the patient developed respiratory insufficiency. CT scan showed progressive consolidations and pleural effusions with septations. Corticosteroid-pulse therapy was given in suspicion of an acute cellular rejection although not proven histologically. Bronchoscopy and BAL did not show an infection. CRP (24 mg/dl) and LDH (528 U/l) increased, so broad spectrum antibiotics and antifungal therapy were given without clinical improvement. AMR was suspected (without DSA or histological findings) and treated as mentioned above. The clinical condition improved completely after two weeks.

Case 3:

The patient showed indications of an infection three weeks after LuTX by fever and FEV1-decline. CRP (30,2 mg/dl) and LDH (383 U/l) elevated. Bronchoscopy, BAL and TBB showed no signs of infection or acute cellular rejection. Probatory antibiotics and corticosteroid-pulse therapy showed no benefit. The patient developed polyserositis in CT scan and respiratory insufficiency. By suspicion of AMR (without DSA and histological findings) the patient was treated as mentioned above with complete clinical response within three weeks.

Summary:

These cases show similar clinical courses of early AMR after LuTX with and without DSA and implicate that AMR can be diagnosed based on clinical findings after exclusion of other causes also in the absence of DSA. Plasmapheresis and IgM-enriched immunoglobulins (Pentaglobulin) seem to be a successful therapeutic strategy.