Clinical Outcomes of Lung Transplantation in the Presence of Donor-Specific Antibodies

Long-term outcomes of sensitized lung transplant recipients after peri-operative desensitization

“…Similar protocols have been adopted by some programs since then; however, this practice remains relatively rare, and sensitized candidates continue to experience prolonged wait times. 9,12 While our published outcomes were reassuring, they were limited by a median posttransplant follow-up time of just 2.1 years. Lack of data on long-term outcomes of patients who are treated with our peri-operative desensitization protocol, or other comparable protocols, may be limiting broader acceptance of this strategy for sensitized lung transplant candidates.…”

“…When surveyed in 2019, several international programs reported using some variation of our desensitization protocol for DSA‐positive lung transplants that involved a combination of PLEX, IVIG, ATG or rituximab, although this practice was often limited to patients who had very limited donor options due to their degree of sensitization or critical illness 9 . Of these programs, Courtwright et al recently reported positive short‐term outcomes for their specific protocol for DSA‐positive, complement‐dependent cytotoxicity crossmatch‐negative lung transplants, which includes postoperative PLEX, in addition to IVIG and rituximab if allograft dysfunction is present 12 . Additionally, some heart transplant programs have also reported safe use of similar peri‐operative desensitization regimens for their DSA‐positive transplants 20,21 …”

“…9 Of these programs, Courtwright et al recently reported positive short-term outcomes for their specific protocol for DSA-positive, complementdependent cytotoxicity crossmatch-negative lung transplants, which includes postoperative PLEX, in addition to IVIG and rituximab if allograft dysfunction is present. 12 Additionally, some heart transplant programs have also reported safe use of similar peri-operative desensitization regimens for their DSA-positive transplants. 20,21 Accepting DSA-positive lung transplants is not yet widespread practice, as evidenced by the significantly lower likelihood of receiving a lung transplant and higher likelihood of dying while on the waitlist among US lung transplant candidates with calculated PRA (cPRA) values exceeding 50%.…”

Novel therapeutic opportunities afforded by plasma cell biology in transplantation

“…Moreover, both pre-existing and de novo IgG DSAs are strongly correlated with allograft injury for all solid organ transplants, including that of the kidney, heart, lung, and liver. [13][14][15][16] Although plasmapheresis and intravenous immunoglobulins (IVIG) are commonly used approaches in several posttransplant protocols against AMR, their efficacy remains transient. 11 Consequently, it is tempting to surmise that in conjunction with currently available immunosuppressive drugs, novel immunotherapy strategies specifically aimed at plasma cells might help improve longterm allograft tolerance.…”

“…Mismatched‐ or non‐HLA molecules on cells of the donor tissue can recruit antibodies as well as other effector immune cells through complement‐dependent and ‐independent pathways, leading to graft thromboses. Moreover, both pre‐existing and de novo IgG DSAs are strongly correlated with allograft injury for all solid organ transplants, including that of the kidney, heart, lung, and liver . Although plasmapheresis and intravenous immunoglobulins (IVIG) are commonly used approaches in several posttransplant protocols against AMR, their efficacy remains transient .…”