Correspondence

Transfer of Peanut Allergy by a Liver Allograft

N Engl J Med 1998; 338:202-203January 15, 1998

Article

To the Editor:

The article “Transfer of Symptomatic Peanut Allergy to the Recipient of a Combined Liver-and-Kidney Transplant,” by Legendre et al. (Sept. 18 issue),1 raises interesting questions about the mechanisms of transfer, the pathophysiology of the allergic reaction in the recipient, and the information provided to patients who receive transplants.

The donor, who had a history of peanut allergy, died of presumed anaphylactic shock due to the ingestion of peanut allergens in satay sauce. Three months after transplantation, the recipient of the liver and right kidney presented with an uncharacterized rash and laryngeal edema after eating peanuts and was found to have anti-peanut IgE antibodies. The authors contend that the allergic reaction of the recipient was probably not due to passive transfer of donor IgE because of the short half-life of serum IgE. They further present evidence of microchimerism in the recipient's skin. We believe that mast cells from the donor's liver were the most likely culprits. The adult liver is a source of mature mast cells, and the fetal liver has been shown to be a source of progenitor mast cells.2,3 Furthermore, cell-bound IgE has a half-life exceeding 120 days.4 Thus, it is entirely feasible that the anti-peanut IgE was derived from the donor. It is also possible that mast cells from the donor either migrated from the liver to the skin or arose from circulating liver-derived precursors, explaining the microchimerism. We can speculate that the donor's liver mast cells were sensitized before death with anti–peanut-specific IgE and three months after transplantation were challenged with peanut in vivo, inducing degranulation and mediator release in the recipient. The symptoms of the recipient were systemic, since they involved two target organs (the skin and the subcutaneous tissues of the larynx) and were most likely due to circulating mediators (histamine and tryptase) released by the liver mast cells. Cutaneous manifestations of anaphylaxis do not necessarily reflect skin mast-cell degranulation.5 Peanut allergy is one of the leading causes of fatal and near-fatal food-induced anaphylaxis.6 No information is available regarding a skin test with peanut allergen in the recipient, which would have helped to define the presence of sensitized skin mast cells derived from either the donor or the recipient.

This case emphasizes the importance of providing transplant recipients with information about the health conditions of organ donors. In this particular case, specific anti-peanut IgE antibodies could have been checked in the recipient's serum without exposing the patient to a life-threatening event.

Mariana Castells, M.D., Ph.D.
Joshua Boyce, M.D.
Brigham and Women's Hospital, Boston, MA 02115

6 References

1. 1

   Legendre C, Caillat-Zucman S, Samuel D, et al. Transfer of symptomatic peanut allergy to the recipient of a combined liver-and-kidney transplant. N Engl J Med 1997;337:822-824
   Full Text | Web of Science | Medline

2. 2

   Irani AA, Craig SS, Nilsson G, Ishizaka T, Schwartz LB. Characterization of human mast cells developed in vitro from fetal liver cells cocultured with murine 3T3 fibroblasts. Immunology 1992;77:136-143
   Web of Science | Medline

3. 3

   Horny HP, Kaiserling E, Campbell M, Parwaresch MR, Lennert K. Liver findings in generalized mastocytosis: a clinicopathologic study. Cancer 1989;63:532-538
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4. 4

   Castells MC, Pascual C, Martin Esteban M, Ojeda JA. Allergy to white potato. J Allergy Clin Immunol 1986;78:1110-1114
   CrossRef | Web of Science | Medline

5. 5

   Bochner BS, Lichtenstein LM. Anaphylaxis. N Engl J Med 1991;324:1785-1790
   Full Text | Web of Science | Medline

6. 6

   Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 1992;327:380-384
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We fully agree with Drs. Castells and Boyce that the transfer of peanut allergy to the recipient may have been mediated by mast-cell–bound IgE. Indeed, in our paper we stated that this possibility could not be ruled out. Whether mast cells, dendritic cells, B cells, or T cells are involved in the case we reported is, however, difficult to ascertain. We would like to add several points to this discussion.

First, the migration of mast cells from the donor's liver to the recipient is possible but difficult to document. In contrast, recent experiments in mice and humans have clearly demonstrated the migration of pluripotential hematopoietic stem cells as well as cells of the dendritic lineage from transplanted organs to the recipient.1 Second, it has been shown in mice that a secondary, hapten-specific IgE antibody response can be achieved by adoptive transfer of primed B or T lymphocytes or both, therefore excluding the need for mast cells in this type of transfer.2 Third, it has been demonstrated that IgE-dependent, antigen-induced anaphylactic death occurred with equal frequency in mast-cell–deficient mice and in normal congenic mice, limiting the role of mast cells in this system.3

Finally, it is conceivable that the allergic symptoms may have been due to the release of several cytokines other than histamine and tryptase. Indeed, cytokines such as tumor necrosis factor α or interleukin-6 can be released from activated cells during an allergic reaction not only by mast cells but also by monocytes and macrophages.

Christophe Legendre, M.D.
Hôpital Saint-Louis, 75010 Paris, France

Sophie Caillat-Zucman, M.D.
Hôpital Necker, 75743 Paris, France

3 References

1. 1

   Taniguchi H, Toyoshima T, Fukao K, Nakauchi H. Presence of hematopoietic stem cells in the adult liver. Nat Med 1996;2:198-203
   CrossRef | Web of Science | Medline

2. 2

   Hamaoka T, Katz DH, Benacerraf B. Hapten-specific IgE antibody responses in mice. II. Cooperative interactions between adoptively transferred T and B lymphocytes in the development of IgE response. J Exp Med 1973;138:538-556
   CrossRef | Web of Science | Medline

3. 3

   Takeishi T, Martin TR, Katona IM, Finkelman FD, Galli SJ. Differences in the expression of the cardiopulmonary alterations associated with anti-immunoglobulin E-induced or active anaphylaxis in mast cell-deficient and normal mice. J Clin Invest 1991;88:598-608
   CrossRef | Web of Science | Medline

Citing Articles (4)

Citing Articles

1. 1

   Yael Levy, Miriam Davidovits, Roxana Cleper, Rivka Shapiro. (2009) New-onset post-transplantation food allergy in children - Is it attributable only to the immunosuppressive protocol?. Pediatric Transplantation 13:1, 63-69
   CrossRef

2. 2

   Imran Khalid, Edward Zoratti, Lisa Stagner, Alan D. Betensley, Hasan Nemeh, Lisa Allenspach. (2008) Transfer of Peanut Allergy From the Donor to a Lung Transplant Recipient. The Journal of Heart and Lung Transplantation 27:10, 1162-1164
   CrossRef

3. 3

   E. Granot, E. Yakobovich, R. Bardenstein. (2006) Tacrolimus immunosuppression - An association with asymptomatic eosinophilia and elevated total and specific IgE levels. Pediatric Transplantation 10:6, 690-693
   CrossRef

4. 4

   Mirna Chehade, Anna Nowak-Wegrzyn, Stuart S. Kaufman, Thomas M. Fishbein, Allan Tschernia, Neal S. LeLeiko. (2004) De Novo Food Allergy After Intestinal Transplantation: A Report of Three Cases. Journal of Pediatric Gastroenterology and Nutrition 38:5, 545-547
   CrossRef