We investigated whether allergen-specific IgE-mediated hypersensitivity is transferred by bone marrow transplantation. Twelve patients, 14 to 47 years of age, undergoing allogeneic bone marrow transplantation for the treatment of hematologic cancer were selected, along with their donors, by a screening questionnaire for a history of atopy in the donor. We evaluated these donor-recipient pairs before transplantation and at several points afterward for immediate skin-test reactivity to 17 allergens. For allergens for which pretransplantation skin tests had been positive in the donors and negative in the recipients, 20 of 46 post-transplantation skin tests were positive in 8 of the 11 recipients who survived for more than one year after transplantation. For allergens for which both donors and recipients had had negative skin tests before transplantation, only 6 of 256 tests (2.3 percent) were positive in the recipients after transplantation. Long-term transfer of donor-derived mite-specific IgE was demonstrated by radioallergosorbent testing in two recipients. Seven recipients either acquired or had an exacerbation of allergic rhinitis, and two recipients without a history of asthma had asthma one year after transplantation. We conclude that allergen-specific IgE-mediated hypersensitivity is adoptively transferred by bone marrow transplantation from donor to recipient by B cells with allergen-specific memory.

Adoptive transfer of allergen-specific immunoglobulin E (IgE) from atopic donors to nonatopic recipients occurs during the first year following bone marrow transplantation (BMT). Mature B-and T-cell clones with allergen-specific memory and hematopoietic progenitor cells are transferred through BMT. The objective of this study was to characterize the long-term rate of allergic sensitization and development of clinical allergic diseases following BMT from atopic donors. A long-term follow-up study was conducted in a cohort of donor and recipient pairs with moderate-to-severe allergic disease in the donor prior to BMT. Assessments of allergen-specific IgE, clinical rhinitis, and asthma were made in the donors prior to BMT and in the recipients with a mean follow-up of 15.5 years after BMT. From an initial cohort of 12 bone marrow transplant recipients who received marrow from allergic donors, 5 long-term survivors were identified. Allergen-specific IgE transferred from donor to recipient following BMT frequently persisted, and a high rate of de novo allergic sensitization was observed between 1 and 14 years after BMT. These events were associated with elevation in total IgE, and development of allergic rhinitis and asthma at long-term follow-up. We conclude that marrowderived immune cells from allergic donors can transfer the predisposition to allergy and asthma. IntroductionAsthma and allergic diseases result from genetic and environmental influences. A unique opportunity to understand the development of asthma and allergy occurs during bone marrow transplantation (BMT) when recipients without allergic disease receive immune cells from allergic donors. We previously showed that recipients undergoing BMT from donors with moderate-to-severe allergic disease had a high rate of acquisition of donor allergen-specific immunoglobulin E (IgE) in the first year after transplantation consistent with adoptive transfer of B-and/or helper T-cell clones with allergen-specific memory. 1 Although our previous study and a number of case reports 2-6 have documented adoptive transfer of allergen-specific IgE in the first year following BMT from atopic donors, there are no long-term studies identifying the consequences of this initial adoptive transfer of allergen-specific IgE and immune cells during BMT from atopic donors. We conducted a long-term follow-up study more than 14 years after BMT in the same cohort of recipients that had received bone marrow transplants from donors with moderate-to-severe allergic disease and determined the long-term persistence of the IgE response and development of clinical allergic disease in recipients. We found that recipients had a high rate of persistence of transferred allergen-specific IgE, and acquisition of new allergen-specific IgE, elevated total IgE, allergic rhinitis, and asthma. This study suggests that marrow-derived immune cells transfer the predisposition to allergy and asthma and supports the primary role of immune cells in the development of the asthma phenotype. Patients, materials...

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