title: CD16+CD56+ cells are a potential culprit for hematuria in IgA nephropathy.
abstract: BACKGROUND
  Hematuria is the first manifestation of urinary abnormality in immunoglobulin A nephropathy (IgAN). Hematuria has recently been reported as a risk factor for deterioration of renal function; however, its cause remains unknown.
  
  
  METHODS
  We analyzed the surface marker of peripheral blood mononuclear cells before and immediately after tonsillectomy in IgAN patients and controls (chronic tonsillitis or tonsillar hypertrophy) by flow cytometry and investigated the association with hematuria. To prove our hypothesis that NK cells induce hematuria, we administered IL-12, activator of NK cells, to HIGA mice. In addition, we transferred cultured NK cells to nude rats and transferred the CD16(+)CD56(+) cells, including NK cells, that are derived from the peripheral blood of IgAN patients immediately after tonsillectomy to nude rats to assess the hematuria level and renal histology of the recipients. We also performed cytotoxicity assays against glomerular endothelial cells by NK cells.
  
  
  RESULTS
  We found that IgAN patients who showed rapid deterioration of hematuria after tonsillectomy also displayed a significant increase in CD16(+)CD56(+) cells in the peripheral blood immediately after tonsillectomy. Exogenous administration of IL-12 to HIGA mice induced hematuria. Adoptive transfer of either cells of an NK cell line, or of CD16(+)CD56(+) cells derived from IgAN patients, into nude rats induced hematuria in the recipients. In vitro analysis showed that NK cells exert cytotoxic activity toward human glomerular endothelial cells in a dose-dependent manner.
  
  
  CONCLUSIONS
  CD16(+)CD56(+) cells seem to be responsible for hematuria in IgAN.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Iwatani
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nagasawa
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Iio
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mizui
authors.forename: Arata
authors.initials: A
authors.lastname: Horii
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Hidenori
authors.initials: H
authors.lastname: Inohara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000818:Animals; D019002:CD56 Antigen / Q000032:analysis; D002460:Cell Line; D002648:Child; D003601:Cytotoxicity Tests, Immunologic; D042783:Endothelial Cells; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000150:complications* / Q000188:drug therapy; D006417:Hematuria / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000737:chemistry* / Q000187:drug effects / Q000637:transplantation; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008875:Middle Aged; D011184:Postoperative Period; D057234:Preoperative Period; D051381:Rats; D017452:Receptors, IgG / Q000032:analysis; D014068:Tonsillectomy; D014069:Tonsillitis / Q000150:complications / Q000601:surgery; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D019002:CD56 Antigen; D017452:Receptors, IgG; D018664:Interleukin-12