Early immunological changes associated with laryngeal transplantation in a major histocompatibility complex-matched pig model

Abstract

SummaryLaryngeal transplantation is an increasingly viable proposition for patients with irreversible diseases of the larynx. One human transplant has been performed successfully, but many questions remain before routine transplantation can begin. In order to measure the immunological changes in mismatched transplants, it is first necessary to know the immediate combined effects of ischaemia-reperfusion injury (IRI) plus the added insult of major surgery in a fully matched setting. We measured the changes in immunologically active mucosal cells following 3 h of cold ischaemia and 8 h of in situ reperfusion in a major histocompatibility complex (MHC)-matched minipig model (n = 4). Biopsies were prepared for quantitative, multiple-colour immunofluorescence histology. The number of immunologically active cells was significantly altered above (supraglottis) and below (subglottis) the vocal cords following transplantation and reperfusion (P < 0·05, P < 0·001, respectively). However, the direction of the change differed between the two subsites: cell numbers decreased post-transplant in the supraglottis and increased in the subglottis. Despite the statistical evidence for IRI, these changes were less than the large normal inter-and intrapig variation in cell counts. Therefore, the significance of IRI in exacerbating loss of function or rejection of a laryngeal allograft is open to question. Longer-term studies are required.

Laryngeal transplantation in minipigs: early immunological outcomes

“…There was interpig variation in expression of all molecules measured (Tables 2-5 and Figs 1 -3). Differences between epithelial and lamina propria compartments in the levels of expression of molecules on leucocytes were consistent with our previous observations ( [6]; Table 2).…”

“…In our previous studies examining the early effects of ischaemia–reperfusion and surgical injury in a non‐recovery transplant model, significant effects were observed at 8 h after reperfusion, but the magnitude of the effects was less than interpig variation at baseline [6]. Here we report the first detailed analysis of the acute and delayed mucosal immunological response to orthotopic laryngeal transplantation in a recovery model over the first week.…”

Laryngeal transplantation in minipigs: vascular, myologic and functional outcomes

“…We developed an orthotopic laryngeal transplantation in NIH minipigs [20] which mirrored the clinical setting [6] and have previously reported results from the first 8 h after revascularisation of donor larynges in recipient pigs [20]. The present paper is a logical extension of our previous work [18, 20] and is based on the consensus findings of the World’s first symposium on this subject [11]. …”

At the crossroads: mucosal immunology of the larynx

“…In a pig model of laryngeal transplantation, a dense population of DC particularly around the basement membrane has been observed22. Furthermore, the activation status of these cells changed following reperfusion.…”