The administration of alpha-1 antitrypsin (AAT) suppressed acute rejection after lung transplantation in a mouse model. This observation may be of particular relevance for patients with alpha-1 antitrypsin deficiency (AATD).
“It is possible that AATD patients, who receive AAT therapy prior to [lung transplantation], have more profound illness, and therefore therapy continuation for a short period following transplantation could positively impact the post-transplant course,” the authors explained in a study published in Respiratory Research.
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Nakagiri et al showed that mice treated with AAT had increased activity of serum antielastase and a lower proportion of Th1 and Th17 among all Th cells when compared to control mice. Moreover, allografts from mice treated with AAT had less cleaved caspase-3-positive cells.
These results are aligned with previous studies. For instance, other studies have shown that the uncontrolled release of neutrophil elastase and other proteases early after lung transplantation contributes to tissue damage and that AAT is a major inhibitor of elastase.
Also, Th1 and Th17 cells are involved in organ rejection after transplantation. AAT can directly bind to caspase-3 and inhibit its activity in inducing apoptosis.
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However, Nakagiri et al also pointed a number of limitations for their study, including the small number of animals investigated and a relatively high transplantation failure rate causing intraoperative death.
Lung transplantation does not treat the inherited deficiency of AAT in patients with AATD. Therefore, patients with AATD treated with lung transplantation remain at risk of redeveloping emphysema.
The use of AAT therapy directly after lung transplantation may provide additional therapeutic value to these patients due to its anti-inflammatory and immunomodulatory effects. However, dedicated clinical studies are still lacking.
Reference
Nakagiri T, Wrenger S, Sivaraman K, et al. α1-Antitrypsin attenuates acute rejection of orthotopic murine lung allografts. Respir Res. 2021;22(1):295. doi:10.1186/s12931-021-01890-x
