Transplantation Tolerance and Mixed Chimerism – Critical Barrier to Progress in VCA

 

One potential solution to the dilemma of immunosuppression-related risks and considerations in VCA is the induction of transplantation tolerance, defined as long-term, immunosuppression-free allograft acceptance with neither clinical nor histologic evidence of rejection, thereby eliminating the need for immunosuppression altogether, through mixed hematopoietic chimerism (Figure 1). Tolerance may also prevent the development of chronic rejection, which is a significant cause of late solid organ transplantation allograft loss and has recently been reported in a face transplant recipient at 7 years post-VCA[1]. Clinically, tolerance of transplanted kidneys has been achieved in haploidentical donor-recipient pairs through donor bone marrow transplantation (DBMT), which achieved mixed donor-recipient lymphohematopoietic chimerism and immunologic tolerance of the renal allograft [2]. Stable mixed chimerism was not required for tolerance induction in this case – indeed, despite transient mixed chimerism, tolerance of the transplanted kidneys was achieved. In contrast, however, we have shown that VCA, like more antigenic SOT (e.g. lungs [3]) will require stable mixed chimerism to achieve tolerance, especially to the epidermal component which will be of utmost importance in a transplanted hand or face.

1.Lantieri L, Grimbert P, Ortonne N, Suberbielle C, Bories D, Gil-Vernet S, et al. Face transplant: long-term follow-up and results of a prospective open study. Lancet (London, England) [Internet]. 2016Oct1;388(10052):1398–407.

2.Kawai T, Sachs DH, Sprangers B, Spitzer TR, Saidman SL, Zorn E, Tolkoff-Rubin N, Preffer F, Crisalli    K, Gao B, Wong W, Morris H, LoCascio SA, Sayre P, Shonts B, Williams WW Jr, Smith RN, Colvin RB, Sykes M, Cosimi AB. Long-term results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression. Am J Transplant. 2014;14(7):1599-611.

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