Immunoglobulin E Levels Following Allogeneic, Autologous, and Syngeneic Bone Marrow Transplantation: An Indirect Association Between Hyperproduction and Acute Graft-?-Host Disease in Allogeneic BMT

Abstract

Markedly elevated serum IgE levels have been noted following allogeneic bone marrow transplantation (BMT) and have been correlated with graft-v-host disease (GVHD) in several studies. To investigate this phenomenon, we measured serum IgE levels in 387 allogeneic, 143 autologous, and 21 syngeneic BMT recipients before and at intervals after BMT. As a population, allogeneic BMT recipients displayed a biphasic elevation in IgE levels, with peak levels occurring either early (days 15 to 19) or late (days 80 to 89) posttransplant. Only in individuals in whom peak levels occurred early did IgE level correlate with liver disease, histological changes, and overall clinical stage of GVHD. The association of IgE elevation and GVHD does not appear to be direct since recipients of syngeneic (monozygotic twin) grafts had the highest incidence of IgE hyperresponsiveness as well as the highest absolute IgE levels. Similarly, 22 recipients of autologous marrow not treated with 4-hydroperoxycyclophosphamide had elevated IgE levels comparable to those seen in allogeneic graft recipients. We hypothesize that augmented IgE synthesis and its subsequent resolution is the natural consequence of immune reconstitution in the presence of potentially reaginic agents such as antibiotics and infectious agents. As such, IgE hyperresponsiveness in syngeneic graft recipients may reflect the maturational sequence of IgE regulatory elements in the absence of interference by GVHD, GVHD therapy, or minor histocompatibility disparities. The cell populations required for IgE response (T cells, B cells, and antigen-presenting cells) may be reconstituted in advance of the regulatory elements that limit IgE production in healthy subjects. Although this temporal relationship does not appear to hold in allogeneic BMT, the balance between positive and negative factors, which determines the rates of IgE synthesis and catabolism, may be altered by GVHD, infection, and liver dysfunction acting alone or in combination.