Body: Risk assessment for lung transplantation (txp) involving the crossing of antibodies against broadly shared public epitopes, is challenging. This is due to the limitations of the solid-phase assay in the quantitative assessment of antibody strength when time does not permit a prospective crossmatch. We present the cases of two patients—who, despite having pre-formed Bw4 DSAs against donors with varying levels of Bw4 expression—received lung txp and have maintained stable clinical outcomes. These cases support transplanting organs from Bw4/Bw6 heterozygous or Bw4/Bw4 homozygous donors to patients with pre-formed Bw4 DSAs, with close monitoring and IVIG (500 mg/kg) alone.
In the first case (CPRA 85%), low-level pre-formed DSAs against B49 (Bw4) and DQ2 ( <3,000 MFI) were identified. Contrary to our initial assessment of a higher risk associated with Bw4, post-txp anti-DQ2 levels significantly increased, while Bw4 levels decreased and maintained a downward trend over the past six months with only IVIG. Despite complications, including hypoxemic respiratory failure, the DQ2 DSA levels eventually began to decrease, fluctuating from 15,000 down to 3,200 MFI, which correlated with low titer results and negative C1q-binding capability.
The second case (CPRA 76%) involves crossing two moderate-level Bw4 DSAs (B53 and B58) and a total MFI exceeding 5,000, conventionally considered high risk. The immunological risk was assessed as moderate based on individual DSA titers, with the patient responding to IVIG treatment without the need for an aggressive desensitization protocol. After a temporary drop <600 MFI post-transplant, due to transfusion requirements on POD#3, these DSAs significantly increased—exceeding 10,000 for B49 and 4,000 MFI for B58 (both C1q positive). Following this surge, the DSA levels have steadily decreased.
Conclusion: Both cases showed rapid IgG production and high DSA peaks within weeks post-transplant, indicative of transfusion-induced responses. However, they have steadily decreased with periodical IVIG without TPE. The second case requires more follow-up for the long-term impact of antibodies against Bw4/Bw4. As of two months post-txp, low-level Bw4 levels have been maintained, with good graft functions achieved with IVIG alone. These two cases have provided preliminary insights into the impact of crossed Bw4 DSAs on graft outcomes in lung txp, potentially breaking the Bw4 barrier.
