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 Schi stosoma mansoni and patients with atopic dermatitis was studied. Patie nts with parasitic infections or allergic diseases have a higher produ ction of IgE. We found a fourfold increased production of I epsilon RN A in both patient groups as compared to control donors. The increased expression of germ-line transcripts correlates with higher serum IgE l evels. Nested primer polymerase chain reaction was used to generate S mu/S epsilon fragments from DNA of patient peripheral blood mononuclea r cells. Twenty-nine out of fourty sequenced switch fragments had unde rgone direct joining from S mu to S epsilon whereas seven fragments sh owed 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 dou ble 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 sequenti al switching had occurred either via deletions or inversions. Mapping of the breakpoints showed hot spots for recombination within S mu, S g amma 1 and S epsilon. To our knowledge, this is the first in vivo stud y in humans demonstrating that switching to IgE can occur from sequent ial rearrangements via gamma 1, gamma 2 or gamma 4.