title: In vitro immunoglobulin isotype suppression in immunoglobulin A nephropathy.
abstract: IgA nephropathy (IgAN) is characterized by mesangial IgA deposition, and up-regulation of the IgA system is frequently described. This study investigated in vitro immunoglobulin isotype production by peripheral blood mononuclear cells from patients with IgAN and controls, without mitogenic stimulation and under the influence of cell cycle inhibitors and cyclosporin A (CyA). In controls, only IgM production was suppressed by cell cycle inhibitors, and no isotype was affected by CyA. This suppressible IgM production may represent antigen-independent 'natural antibody'. In IgAN, IgM, IgA and IgG were all suppressed by cell cycle inhibitors, and CyA suppressed IgA production. This state of altered immune activation in IgAN demonstrates T-cell-independent IgA production, suggesting that it is IgA 'natural antibody'. In conclusion, we suggest that mesangial IgA deposition may not be antigen dependent but due to some non-immune characteristic of the IgA molecule.
authors.affiliation: Department of Nephrology, Leicester General Hospital, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Allen
authors.forename: L
authors.initials: L
authors.lastname: Layward
authors.forename: S J
authors.initials: SJ
authors.lastname: Harper
authors.forename: J
authors.initials: J
authors.lastname: Feehally
mesh_terms: D000328:Adult; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013936:Thymidine / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D007132:Immunoglobulin Isotypes; D016212:Transforming Growth Factor beta; D016572:Cyclosporine; D013936:Thymidine; D006918:Hydroxyurea