Leukocyte transfusion-associated granulocyte responses in a patient with X-linked hyper-IgM syndrome

X-linked hyper-IgM syndrome (XHIM) is a severe congenital immunodeficiency caused by mutations in CD154 (CD40 ligand, gp39), the T cell ligand for CD4 0 on B cells. Chronic or cyclic neutropenia is a frequent complicating feat ure that heightens susceptibility to severe infections. We describe a patie nt with a variant of XHIM who produced elevated levels of serum IgA as well as IgM and suffered from chronic severe neutropenia. Eight of ten leukocyt e transfusions with cells from a maternal aunt, performed because of mucosa l infections, resulted in similar episodes of endogenous granulocyte produc tion. Transfection studies with the mutant CD154 protein indicate that the protein is expressed at the cell surface and forms an aberrant trimer that does not interact with CD40. The data suggest that allogeneic cells from th e patient's aunt, probably activated T cells bearing functional CD154, may interact with CD40(+) recipient cells to produce maturation of myeloid prec ursors in the bone marrow.