title: Up-regulation of interleukin-4 and CD23/FcepsilonRII in minimal change nephrotic syndrome.
abstract: Although the pathogenesis of childhood minimal change nephrotic syndrome (MCNS) has not been clearly defined, the current hypothesis favors an involvement of T cell dysfunction. The symptom onset and the relapse of MCNS are frequently associated with allergy and increased IgE levels in sera. Since a T cell-derived cytokine interleukin-4 (IL-4) plays a key role in the regulation of IgE production and allergic response, we investigated the role of IL-4 in the pathophysiology of MCNS. Using fluorescence-activated cell scanning we observed a significantly higher expression of CD23, the type II IgE receptor (FcepsilonRII), on fresh B cells from active MCNS patients (n=22) compared with age-matched healthy normal controls (n=12). The upregulation of CD23 correlates with greater IL-4 activity in the culture supernatant of MCNS peripheral blood lymphocytes (PBLs) than normal PBLs stimulated by mitogens, as assessed by the CD23-inducing effect of the PBL supernatant on tonsillar B cells. Furthermore, Northern blot and reverse transcription-based polymerase chain reaction analysis have revealed significantly elevated levels of IL-4 mRNAs both in mitogen-stimulated and unstimulated MCNS PBLs, compared with healthy normals or disease controls with other renal disorders. Together these results strongly suggest that the upregulation of IL-4 in T cells may be part of the T cell dysfunction involved in MCNS.
authors.affiliation: Department of Pediatrics, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: B S
authors.initials: BS
authors.lastname: Cho
authors.forename: S R
authors.initials: SR
authors.lastname: Yoon
authors.forename: J Y
authors.initials: JY
authors.lastname: Jang
authors.forename: K H
authors.initials: KH
authors.lastname: Pyun
authors.forename: C E
authors.initials: CE
authors.lastname: Lee
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D019138:Antibodies, Blocking / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015152:Blotting, Northern; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009402:Nephrosis, Lipoid / Q000188:drug therapy / Q000378:metabolism*; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000096:biosynthesis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000305:Adrenal Cortex Hormones; D019138:Antibodies, Blocking; D017077:Culture Media, Conditioned; D008934:Mitogens; D012333:RNA, Messenger; D017455:Receptors, IgE; D015847:Interleukin-4