Letter to the Editor

Bone Marrow Transplantation (2014) 49, 993–994; doi:10.1038/bmt.2014.95; published online 28 April 2014

Peanut allergy transferred by BMT

W Ip1, C Cale2, P Veys3 and W Qasim1,2

  1. 1Molecular Immunology Unit, Institute of Child Health, London, UK
  2. 2Department of Immunology, Great Ormond Street Hospital NHS Foundation Trust, London, UK
  3. 3Bone Marrow and Blood Stem Cell Transplant Unit, Great Ormond Street Hospital NHS Foundation Trust, London, UK

Correspondence: W Ip, E-mail: w.ip@ucl.ac.uk

Suspected transfer of peanut allergy has been sporadically reported after solid organ transplantation of cadaveric lung or liver grafts collected from donors with documented allergy histories.1,2 Here we report likely transfer of peanut allergy following leukocyte-replete BMT from a HLA-matched sibling donor.

A 1-month-old South Asian male infant with homozygous RMRP gene mutation (35 C>A) and family history of severe combined immunodeficiency underwent an unconditioned cord blood transplant from an older sibling. The donor was known to have significant peanut allergy since the age of 2 years and maintained dietary exclusion. The transplant was complicated by retarded kinetics of cellular immune reconstitution resulting in adenovirus reactivation and widespread molluscum contagiosum. Donor chimerism was initially restricted to the T-cell lineage and a second transplant with BM stem cells from the original donor was performed at 20 months of age with conditioning comprising fludarabine 30mg/m2 (days −7 to −3) and melphalan 140mg/m2 (day −2), and prophylaxis against GVHD with CYA and mycophenolate mofetil. The donor was 4 years 6 months old at the time of the second transplant. Serotherapy was not administered, both grafts were infused without manipulation and were leukocyte replete. High-level T-cell (70%) and mixed, myeloid (18%) and B-cell (25%) chimerism was achieved after the second transplant, and was associated with clearance of viral infections, including molluscum. EBV reactivation at 5 months post transplant was treated with a single dose of rituximab (375mg/m2). Grade I stage 1 skin GVHD developed after 3 months and was controlled with topical steroids. CYA was discontinued 8 months after the transplant. Approximately 12 months later (aged 2 years 8 months), the subject presented with facial rash and angioedema shortly after ingestion of a peanut-containing breakfast cereal, suggestive of acute allergic reaction. After his first transplant he had regularly tolerated nuts and peanuts, including this specific cereal without adverse reactions. On first resuming intake of the same cereal after his second transplant, the subject developed allergic symptoms. The subject’s skin prick test showed positive wheal responses to peanut (10mm) and cashew nut (8mm) (positive control 3mm, negative control 0mm; almond, hazelnut and walnut 0mm). Total serum IgE was not elevated (44kU/L) but specific IgE for peanut was high at 24.6kUA/L. Elevated levels of specific IgE to peanut storage protein Ara h1 and Ara h6 were detected. Further investigations found that the sibling BM donor also had elevated specific IgEs for peanut Ara h1 and Ara h6, as well as against Ara h2 and h3; cashew Ana o2, walnut Jug R1, r2 and soybean Glym6. There have been several reports of transfer of aeroallergen-specific IgE and asthma/rhinitis following haematopoietic SCT from atopic donors (both related and unrelated donors) and non-atopic donors;1,3 however, this is the first report using allergen component-resolved diagnostics (CRD). Transfer of nut allergy with confirmatory-specific IgE tests in both donor and recipient has also been documented,4 and we have previously reported resolution of peanut allergy following SCT and speculated that ablation of host B cells during conditioning had eradicated IgE-producing populations.5 Similarly, several theories have been proposed to account for the mechanism of allergy transfer after transplantation. Presentation of peanut allergy following solid organ transplantation has occurred within days or weeks of grafting,1,2 raising the possibility of specific IgE transfer via the graft. Whereas unbound IgE has a short half-life (2–4 days), mast cells with surface-bound IgE may persist for longer (up to 3 weeks),1 allowing delayed manifestations. In the allo-SCT setting, transfer of allergen-specific memory T cells or B cells (producing specific IgEs) from allergic donors are probably more relevant, but the situation is complicated by the observations following transplantation from non-atopic donors where recipients develop allergic manifestations during a period of complex immune dysregulation.6 Allergy has been attributed to immune reconstitution via Th2 bias pathways, and has been linked to the development of GVHD as well as virus-induced tissue damage after allo-SCT.7 A survey of allergies following SCT has suggested that cord blood grafts may be associated with increased risks of allergic complications,8 although such studies can be difficult to interpret given that underlying shared genetics (including HLA types) may predispose to allergy. In our patient, the delayed timing of the allergy and the detection of highly specific peanut allergen IgE, which are also detectable in the donor, suggest transfer of allergen-specific lymphocytes during transplantation. Usually, serotherapy with agents such as alemtuzemab or anti-thymocyte globulin is administered to recipients as part of their preparative conditioning regimen, and has a key role in lymphodepleting grafts following infusion. In our subject, serotherapy was omitted given the high degree of HLA matching and concerns relating to pre-existing viral infections. This may have allowed for the ready transfer of memory T and B cells capable of producing allergen-specific IgE. While initial B-cell reconstitution (on day 229 post transplant) following the second procedure was slowed by the use of rituximab (day 126) for EBV reactivation, by the time the symptoms of peanut allergy developed around day 300, B-cell numbers in the peripheral circulation were normal albeit with mixed chimerism.

This case provides rarely available evidence of the transferability of specific allergy by transplantation and highlights the power of CRD in tracking allergy transfer. CRD uses pure allergen proteins, produced by purification from natural allergen sources or recombinant expression of allergen-encoding complementary DNA and several studies have demonstrated that CRD improves the specificity of allergy testing.9 The laboratory data provide compelling evidence that the allergy was adoptively transferred in this case, and although there is a possibility that the condition arose spontaneously in a host environment genetically predisposed to allergy development, neither the parents nor the three other siblings had a history of food allergy.

We recommend careful communication of known allergies ahead of transplantation and advise that recipients and their clinicians be alerted to the possibility of specific reactions where significant donor allergies have been defined.

Top

Conflict of interest

The authors declare no conflict of interest.

Top

References

  1. Khan F, Hallstrand TS, Geddes MN, Henderson Jr WR, Storek J. Is allergic disease curable or transferable with allogeneic hematopoietic cell transplantation? Blood 2009; 113: 279–290. | Article | PubMed | ISI | CAS |
  2. Schuller A, Barnig C, Matau C, Geny S, Gosselin M, Moal MC et al. Transfer of peanut allergy following lung transplantation: a case report. Transplantat Proc 2011; 43: 4032–4035. | Article |
  3. Storek J, Vliagoftis H, Grizel A, Lyon AW, Daly A, Khan F et al. Allergy transfer with hematopoietic cell transplantation from an unrelated donor. Bone Marrow Transplant 2011; 46: 605–606. | Article | PubMed |
  4. Tucker J, Barnetson RS, Eden OB. Atopy after bone marrow transplantation. Br Med J 1985; 290: 116–117. | Article |
  5. Hourihane JO, Rhodes HL, Jones AM, Veys P, Connett GJ. Resolution of peanut allergy following bone marrow transplantation for primary immunodeficiency. Allergy 2005; 60: 536–537. | Article | PubMed |
  6. Shalit M, Amar A, Or R. Allergy development after bone marrow transplantation from a non-atopic donor. Clin Exp Allergy 2002; 32: 1699–1701. | Article | PubMed | ISI | CAS |
  7. Gennery AR, Cant AJ. Development of allergy post-bone marrow transplantation. Clin Exp Allergy 2002; 32: 1677–1678. | Article | PubMed | ISI | CAS |
  8. Vaughan LA, Vu M, Sengsayadeth S, Lucid C, Clifton C, McCarty K et al. New allergies after cord blood transplantation. Cytotherapy 2013; 15: 1259–1265. | Article | PubMed |
  9. Kattan JD, Wang J. Allergen component testing for food allergy: ready for prime time? Curr Allergy Asthma Rep 2013; 13: 58–63. | Article | PubMed |
Top

Acknowledgements

This work was supported by Great Ormond Street Hospital Children’s Charity and Department of Health’s National Institute for Health Research Biomedical Research Centre's funding scheme via GOSH BRC.