title: IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells.
abstract: BACKGROUND
  Circulating immune complexes (CIC) containing galactose (Gal)-deficient IgA1 from adults with IgA nephropathy (IgAN) induce proliferation of cultured mesangial cells, but activities of CIC from pediatric patients with the disease have not been studied.
  
  
  METHODS
  CIC of different sizes were isolated from sera of pediatric and adult IgAN patients and their effects on cultured human mesangial cells (MC) were assessed by measuring cellular proliferation, expression of IL-6 and IL-8 and laminin and phosphotyrosine signaling.
  
  
  RESULTS
  Large CIC from pediatric IgAN patients (>800 kDa) containing Gal-deficient IgA1 stimulated cellular proliferation, whereas in some patients, smaller CIC were inhibitory. Addition of stimulatory and inhibitory CIC to MC differentially altered phosphorylation patterns of three major tyrosine-phosphorylated proteins of molecular mass 37, 60 and 115 kDa. The stimulatory CIC transiently increased tyrosine-phosphorylation of the 37-kDa protein and decreased phosphorylation of the other two proteins, whereas the inhibitory CIC increased phosphorylation of all three proteins. Furthermore, we investigated the influence of IgA1-containing CIC from sera of children with IgAN with clinically active disease (i.e., abnormal urinalysis and/or serum creatinine concentration) or inactive disease (i.e., normal urinalysis and serum creatinine concentration) on the expression of IL-6 and IL-8 genes by mesangial cells. Real-time reverse transcription-polymerase chain reaction results showed that the CIC from a patient with active disease stimulated MC to express the two cytokine genes at higher levels than did the CIC from a patient with inactive disease. Moreover, stimulatory CIC increased production of the extracellular matrix protein laminin.
  
  
  CONCLUSIONS
  These data indicate that sera of pediatric IgAN patients contain biologically active CIC with Gal-deficient IgA1.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA. jannovak@uab.edu
authors.forename: Jan
authors.initials: J
authors.lastname: Novak
authors.forename: Leona
authors.initials: L
authors.lastname: Raskova Kafkova
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Milan
authors.initials: M
authors.lastname: Tomana
authors.forename: Karel
authors.initials: K
authors.lastname: Matousovic
authors.forename: Rhubell
authors.initials: R
authors.lastname: Brown
authors.forename: Stacy
authors.initials: S
authors.lastname: Hall
authors.forename: John T
authors.initials: JT
authors.lastname: Sanders
authors.forename: T Matthew
authors.initials: TM
authors.lastname: Eison
authors.forename: Zina
authors.initials: Z
authors.lastname: Moldoveanu
authors.forename: Lea
authors.initials: L
authors.lastname: Novak
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Novak
authors.forename: Richard
authors.initials: R
authors.lastname: Mayne
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Julian
authors.forename: Jiri
authors.initials: J
authors.lastname: Mestecky
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wyatt
mesh_terms: D000293:Adolescent; D000328:Adult; D000936:Antigen-Antibody Complex / Q000097:blood / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005690:Galactose / Q000172:deficiency; D005919:Glomerular Filtration Rate; D005920:Glomerular Mesangium / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000503:physiopathology*; D006031:Glycosylation; D006801:Humans; D007124:Immunoenzyme Techniques; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D005690:Galactose