Direct and sequential switching from mu to epsilon in patients with Schistosoma mansoni infection and atopic dermatitis

Immunoglobulin isotype switching to IgE in patients infected with Schistosoma mansoni and patients with atopic dermatitis was studied. Patients with parasitic infections or allergic diseases have a higher production of IgE. We found a fourfold increased production of I epsilon RNA in both patient groups as compared to control donors. The increased expression of germ-line transcripts correlates with higher serum IgE levels. Nested primer polymerase chain reaction was used to generate S mu/S epsilon fragments from DNA of patient peripheral blood mononuclear cells. Twenty-nine out of fourty sequenced switch fragments had undergone direct joining from S mu to S epsilon whereas seven fragments showed mono sequential switching from S mu via either S mu, S gamma 2, S gamma 4 or S epsilon to S epsilon and four fragments demonstrated double sequential switch: S mu/S mu/S gamma 1/S epsilon, S mu/S gamma 2/S epsilon/S epsilon or S mu/S gamma 1/S gamma 2/S epsilon. The sequential switching had occurred either via deletions or inversions. Mapping of the breakpoints showed hot spots for recombination within S mu, S gamma 1 and S epsilon. To our knowledge, this is the first in vivo study in humans demonstrating that switching to IgE can occur from sequential rearrangements via gamma 1, gamma 2 or gamma 4.