title: Direct and sequential switching from mu to epsilon in patients with Schistosoma mansoni infection and atopic dermatitis.
abstract: 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 four-fold 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 gamma2, S gamma4 or S epsilon to S epsilon and four fragments demonstrated double sequential switch: S mu/S mu/S gamma1/S epsilon, S mu/S gamma2/S epsilon/S epsilon or S mu/S gamma1/ S gamma2/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 gamma1 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 gamma1, gamma2 or gamma4.
authors.affiliation: Center for Biotechnology, NOVUM, Karolinska Institute, Huddinge, Sweden. Berivan.Baskin@cbt.ki.se
authors.forename: B
authors.initials: B
authors.lastname: Baskin
authors.forename: K B
authors.initials: KB
authors.lastname: Islam
authors.forename: B
authors.initials: B
authors.lastname: Evengård
authors.forename: L
authors.initials: L
authors.lastname: Emtestam
authors.forename: C I
authors.initials: CI
authors.lastname: Smith
mesh_terms: D001483:Base Sequence; D003876:Dermatitis, Atopic / Q000276:immunology*; D015870:Gene Expression; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005812:Genes, Switch; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics*; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011995:Recombination, Genetic; D012555:Schistosomiasis mansoni / Q000276:immunology*
chemical_list: D007075:Immunoglobulin M; D007139:Immunoglobulin epsilon-Chains; D007148:Immunoglobulin mu-Chains; D012333:RNA, Messenger; D007073:Immunoglobulin E