Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Curability and transferability of atopy with allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 55, pages 1282–1289 (2020)Cite this article

Subjects

This article has been updated

Abstract

Atopy is excessive production of IgE in response to allergens. We evaluated in patients undergoing allogeneic hematopoietic cell transplantation (HCT) the following hypotheses: (1) Atopy is “curable” in atopic patients receiving HCT from a nonatopic donor (D-R+), and (2) Atopy is transferable from atopic donors to nonatopic recipients (D+R-). Atopic patients with atopic donors (D+R+) and non-atopic patients with non-atopic donors (D-R-) served as controls. We measured levels of multiallergen-specific IgE (A-IgE, atopy defined as ≥0.35 kUA/L) in sera from 54 patients and their donors pre HCT and from the patients at ≥2 years post HCT. Only 7/12 (58%) D− R+ patients became nonatopic after HCT. Only 1/11 (9%) D+R- patients became atopic. Eleven of 13 (85%) D-R- patients remained nonatopic. Unexpectedly, 11/18 (61%) D+R+ patients became nonatopic. In conclusion, contrary to our hypothesis and previous reports, the “cure” of atopy may occur in only some D-R+ patients and the transfer of atopy may occur rarely. The “cure” may not be necessarily due to the exchange of atopic for nonatopic immune system, as the “cure” may also occur in D+R+ patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: A-IgE levels before and after HCT in D-R+ and D-R- patients.
Fig. 2: A-IgE levels before and after HCT in D+R- and D+R+ patients.

Similar content being viewed by others

Change history

  • 17 April 2020

    The original version of this Article was updated shortly after publication to correct the typo in the title where ‘Curability’ was misspelled as ‘Curtability. The update does not impact on the scientific content of the article. This has now been corrected in both the PDF and HTML versions of the Article.

  • 20 May 2020

    The original version of this Article was updated shortly after publication for minor correction on the legend of supplementary figure 9. The update does not impact on the scientific content of the article.

References

  1. Szefler SJ, Wenzel S, Brown R, Ezurum SC, Fahy JV, Hamilton RG, et al. Asthma outcomes: biomarkers. J Allergy Clin Immunol. 2012;129:S9–23.

    Article  Google Scholar 

  2. Thomsen SF. Epidemiology and natural history of atopic diseases. Eur Clin Respir J. 2015;2. https://doi.org/10.3402/ecrj.v2.24642.

  3. Adkinson NF, Yunginger JW, Busse WW, Bochner BS, Holgate ST, Simons FER. Middleton’s allergy. Philadelphia: Mosby; 2003.

  4. Foley SC, Prefontaine D, D’Antoni M, Hamid Q. Images in allergy and immunology: regulatory T cells in allergic disease. J Allergy Clin Immunol. 2007;120:482–6.

    Article  CAS  Google Scholar 

  5. Hartl D, Koller B, Mehlhorn AT, Reinhardt D, Nicolai T, Schendel DJ, et al. Quantitative and functional impairment of pulmonary CD4+CDS5hi regulatory T cells in pediatric asthma. J Allergy Clin Immunol. 2007;119:1258–66.

    Article  CAS  Google Scholar 

  6. Hackett TL, Knight DA. The role of epithelial injury and repair in the origins of asthma. Curr Opin Allergy Clin Immunol. 2007;7:63–8.

    Article  Google Scholar 

  7. Walker SA, Riches PG, Wild G, Ward AM, Shaw PJ, Desai S, et al. Total and allergen-specific IgE in relation to allergic response pattern following bone marrow transplantation. Clin Exp Immunol. 1986;66:633–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Bellou A, Kanny G, Fremont S, Moneret-Vautrin DA. Transfer of atopy following bone marrow transplantation. Ann Allergy Asthma Immunol. 1997;78:513–6.

    Article  CAS  Google Scholar 

  9. Saarinen UM. Transfer of latent atopy by bone marrow transplantation? A case report. J Allergy Clin Immunol. 1984;74:196–200.

    Article  CAS  Google Scholar 

  10. Tucker J, Barnetson RSC. Atopy after bone marrow transplantation. Brit Med J. 1985;290:116–7.

    Article  CAS  Google Scholar 

  11. Smith SR, MacFarlane AW, Lewis-Jones MS. Papular urticaria and transfer of allergy following bone marrow transplantation. Clin Exp Dermatol. 1988;13:260–2.

    Article  CAS  Google Scholar 

  12. Yong PF, Grosse-Kreul D, Devereux S, Pagliuca A, Maher J, Ibrahim MA. Increase in allergy following donor lymphocyte infusions. Bone Marrow Transpl. 2006;37:983–4.

    Article  CAS  Google Scholar 

  13. Agosti JM, Sprenger JD, Lum LG, Witherspoon RP, Fisher LD, Storb R, et al. Transfer of allergen-specific IgE-mediated hypersensitivity with allogeneic bone marrow transplantation. N. Engl J Med. 1988;319:1623–8.

    Article  CAS  Google Scholar 

  14. Hinterberger W, Hinterberger-Fischer M, Marmont A. Clinically demonstrable anti-autoimmunity mediated by allogeneic immune cells favorably affects outcome after stem cell transplantation in human autoimmune diseases. Bone Marrow Transpl. 2002;30:753–9.

    Article  CAS  Google Scholar 

  15. Wahn V, Laws HJ, Bode CP, Burdach SE. Cure of latex allergy by bone marrow transplantation. Eur J Pediatr. 1999;158:88.

    Article  CAS  Google Scholar 

  16. Koharazawa H, Kanamori H, Takabayashi M, Yamaji S, Taguchi J, Fujimaki K, et al. Resolution of atopic dermatitis following allogeneic bone marrow transplantation for chronic myelogenous leukemia. Bone Marrow Transpl. 2005;35:1223–4.

    Article  CAS  Google Scholar 

  17. Hourihane JO, Rhodes HL, Jones AM, Veys P, Connett GJ. Resolution of peanut allergy following bone marrow transplantation for primary immunodeficiency. Allergy. 2005;60:536–7.

    Article  Google Scholar 

  18. Zeng G, Hu H, Zheng P, Wu G, Wei N, Liang X. The practical benefit of Phadiatop test as the first-line in vitro allergen-specific immunoglobulin E (sIgE) screening of aeroallergens among Chinese asthmatics: a validation study. Ann Transl Med. 2018;6:151.

    Article  Google Scholar 

  19. Cantani A, Ferrara M, Barbieri C, Monteleone A, Businco L. Evaluation of new test (Phadiatop) for the screening of respiratory allergic disorders in children. Ann Allergy. 1990;64:158–61.

    CAS  PubMed  Google Scholar 

  20. Hwang H, Kwon J, Kim JY, Lee HH, Oh CE, Choi GS. The RIDA allergy screen versus the phadiatop test in 430 consecutive patient specimens. Lab Med. 2016;47:20–9.

    Article  Google Scholar 

  21. Heyd J, Donnenberg AD, Burns WH, Saral R, Santos GW. Immunoglobulin E levels following allogeneic, autologous, and syngeneic bone marrow transplantation: an indirect association between hyperproduction and acute graft-v-host disease in allogeneic BMT. Blood. 1988;72:442–6.

    Article  CAS  Google Scholar 

  22. Brenner MK. Recovery of Ig isotypes following T cell depleted allogeneic bone marrow transplantation. Brit J Haematol. 1986;64:25.

    Article  Google Scholar 

  23. Ringden O. Markedly elevated serum IgE levels following allogeneic and syngeneic bone marrow transplantation. Blood. 1983;61:1190.

    Article  CAS  Google Scholar 

  24. Bosch M, Khan F, Storek J. Immune reconstitution after hematopoietic cell transplantation. Curr Opin Hematol. 2012;19:324–35.

    Article  Google Scholar 

  25. Burt RK, Traynor A, Statkute L, Barr WG, Rosa R, Schroeder J, et al. Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus. JAMA. 2006;295:527–35.

    Article  CAS  Google Scholar 

  26. Tsukamoto H, Nagafuji K, Horiuchi T, Mitoma H, Niiro H, Arinobu Y. Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4+ T cells. Rheumatology. 2011;50:944–52.

    Article  CAS  Google Scholar 

  27. Swart JF, Delemarre EM, van Wijk F, Boelens JJ, Kuball J, van Laar JM, et al. Haematopoietic stem cell transplantation for autoimmune diseases. Nat Rev Rheumatol. 2017;13:244–56.

    Article  CAS  Google Scholar 

  28. De Amici M, Ciprandi G. The age impact on serum total and allergen-specific IgE. Allergy Asthma Immunol Res. 2013;5:170–4.

    Article  Google Scholar 

  29. Mediaty A, Neuber K. Total and specific serum IgE decreases with age in patients with allergic rhinitis, asthma and insect allergy but not in patients with atopy dermatitis. Immun Ageing. 2005;2:9.

    Article  Google Scholar 

  30. Ulrik CS, Backer V. Atopy in Danish children and adolescents: results from a longitudinal population study. Ann Allergy Asthma Immunol. 2000;85:293–7.

    Article  CAS  Google Scholar 

  31. Oryszczyn MP, Annesi I, Neukirch F, Doré MF, Kauffmann F. Longitudinal observations of serum IgE and skin prick test response. Am J Respir Crit Care Med. 1995;151:633–8.

    Google Scholar 

  32. Mohty M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia. 2007;21:1387–94.

    Article  CAS  Google Scholar 

  33. Leitner J, Grabmeier-Pfistershammer K, Majdic O, Zlabinger G, Steinberger P. Interaction of antithymocyte globulins with dendritic cell antigens. Am J Transpl. 2011;11:138–45.

    Article  CAS  Google Scholar 

  34. Storek J, Vliagoftis H, Grizel A, Lyon AW, Daly A, Khan F, et al. Allergy transfer with hematopoietic cell transplantation from an unrelated donor. BMT. 2011;46:605–6.

    CAS  Google Scholar 

  35. Luger EO, Fokuhl V, Wegmann M, Abram M, Tillack K, Achatz G, et al. Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge. J Allergy Clin Immunol. 2009;124:819–26.

    Article  CAS  Google Scholar 

  36. Mitre E, Nutman TB. IgE memory: persistence of antigen-specific IgE responses years after treatment of human filarial infections. J Allergy Clin Immunol. 2006;117:939–45.

    Article  CAS  Google Scholar 

  37. Bhoj VG, Arhontoulis D, Wertheim G, Capobianchi J, Callahan CA, Ellebrecht CT, et al. Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood. 2016;128:360–70.

    Article  CAS  Google Scholar 

  38. Griffith LM, McCoy JP Jr, Bolan CD, Stroncek DF, Pickett AC, Linton GF, et al. Persistence of recipient plasma cells and anti-donor isohaemagglutinins in patients with delayed donor erythropoiesis after major ABO incompatible non-myeloablative haematopoietic cell transplantation. Br J Haematol. 2005;128:668–75.

    Article  CAS  Google Scholar 

  39. Gerritsen EJA, van Tol MJD, Lankester AC, van der Weijden-Ragas CPM, Jol-van der Zijde CM, Ouderman-Gruber NJ, et al. Immunoglobulin levels and monoclonal gammopathies in children after bone marrow transplantation. Blood. 1993;82:3493–502.

    Article  CAS  Google Scholar 

  40. KleinJan A, Vinke JG, Severijnen LW, Fokkens WJ. Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients. Eur Respir J. 2000;15:491–7.

    Article  CAS  Google Scholar 

  41. Happel CS, Stone KD, Freeman AF, Shah NN, Wang A, Lyons JJ, et al. Food allergies can persist after myeloablative hematopoietic stem cell transplantation in dedicator of cytokinesis 8-deficient patients. J Allergy Clin Immunol. 2016;137:1895–8.e5.

    Article  Google Scholar 

  42. Slott RI, Zweiman B. A controlled study of the effect of corticosteroids on immediate skin test reactivity. J Allergy Clin Immunol. 1974;54(4):229–34.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are extremely grateful for the dedication of the research nurses including Krista Dyck, Jennifer LeBlanc, Candice Healey, and Polly Louie, and the research coordinators including Mamta Kantharia and Heather Cooper. We wish to thank Cindy Miskolczi-McCallum for her assistance. We also thank the staff of Calgary Laboratory Services including Lori Gervais, Patricia Johnson, and Rhonda Jackson. We thank the Foothills Medical Center leukemia ward nurses headed by Laura Spilchen and Lorraine Harrison. We thank the staff of the CIBMTR (Center for International Blood and Marrow Transplant Research) Research Sample Repository, who provided donor pretransplant specimens on three cases. The study was funded by a grant from Alberta Heritage Foundation for Medical Research, a grant from Calgary Lab Services/Alberta Public Laboratories, and a grant from Buckley Family Foundation.

Funding

The study was funded by a grant from Alberta Heritage Foundation for Medical Research, a grant from Calgary Lab Services/Alberta Public Laboratories, and a grant from Buckley Family Foundation.

Author information

Authors and Affiliations

  1. University of Calgary, Calgary, AB, Canada

    Sarah Whiteside, Alex Chin, Gaurav Tripathi, Poonam Dharmani-Khan, Michelle N. Geddes, Victor Lewis, Monica Modi, Amit Kalra, Rosy Dabas, Ariz Akhter, Richard Leigh, Andrew Daly, Faisal M. Khan & Jan Storek

  2. Alberta Public Laboratories, Calgary, AB, Canada

    Alex Chin & Faisal M. Khan

  3. Alberta Health Services, Calgary and Edmonton, AB, Canada

    Gaurav Tripathi, Poonam Dharmani-Khan, Michelle N. Geddes, Victor Lewis, Loree Larratt, Tiffany van Slyke, Joseph Brandwein, Richard Leigh, Andrew Daly & Jan Storek

  4. Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    Marketa Markova

  5. 2nd Faculty of Medicine, Charles University, Prague, Czech Republic

    Petra Keslova & Petr Sedlacek

  6. University of Alberta, Edmonton, AB, Canada

    Loree Larratt, Tiffany van Slyke & Joseph Brandwein

  7. Immunobiology Research, Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA

    Stephen R. Spellman

Authors
  1. Sarah Whiteside
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alex Chin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gaurav Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Poonam Dharmani-Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marketa Markova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Petra Keslova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Petr Sedlacek
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michelle N. Geddes
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Victor Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Monica Modi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Amit Kalra
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Rosy Dabas
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ariz Akhter
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Loree Larratt
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Tiffany van Slyke
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Joseph Brandwein
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Stephen R. Spellman
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Richard Leigh
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Andrew Daly
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Faisal M. Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jan Storek
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Contribution: SW analyzed the data and wrote the manuscript. AC supervised the A-IgE determination. GT, RD, and AA performed chimerism analysis. PD-K and AK enumerated CD4 T cells. MM, PK, PS, MNG, VL, MM, LL, AD, TVS, JB, and SS facilitated patient accrual and collection of specimens. RL and FMK provided intellectual input. JS designed the study, supervised the analyses and edited the manuscript.

Corresponding author

Correspondence to Sarah Whiteside.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Whiteside, S., Chin, A., Tripathi, G. et al. Curability and transferability of atopy with allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 55, 1282–1289 (2020). https://doi.org/10.1038/s41409-020-0876-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-0876-7

Search

Advanced search

Quick links