title: Induction of anti-carbonic-anhydrase-II antibody causes renal tubular acidosis in a mouse model of Sjogren's syndrome.
abstract: OBJECTIVE
  We recently reported that renal tubular acidosis (RTA) in Sjogren's syndrome (SjS) is associated with high titers of an autoantibody against carbonic anhydrase (CA) II, an important enzyme in renal acid-base regulation. The purpose of this study was to determine whether a CA-II antibody could cause RTA in a mouse model of SjS.
  
  
  METHODS
  PL/J mice were immunized with human CA II to induce CA II antibody formation, whereas controls were injected with phosphate-buffered saline and adjuvant. After 6 weeks, anti-CA-II antibody titers were measured, then ammonium chloride was administered orally for 1 week to detect any acidification defect.
  
  
  RESULTS
  CA-II-immunized mice showed higher anti-CA-II antibody titers than control mice. Pathologically, lymphocytic and plasma cell infiltration was seen in the salivary glands and kidneys of CA-II-immunized mice, but not in controls. On acid loading, blood pH and urine pH decreased in both groups of mice, but the slope of urine pH versus blood pH was less steep in the CA-II-immunized mice, suggesting that these mice had an impaired ability to reduce their urine pH in the face of metabolic acidosis.
  
  
  CONCLUSIONS
  CA-II-immunized mice had a urinary acidification defect, which may be similar to that seen in patients with SjS.
authors.affiliation: Kidney Center, Toranomon Hospital, Tokyo, Japan. ftakemoto-ind@umin.ac.jp
authors.forename: Fumi
authors.initials: F
authors.lastname: Takemoto
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Katori
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Hoshino
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suwabe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sogawa
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nomura
authors.forename: Shohei
authors.initials: S
authors.lastname: Nakanishi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Higa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanbayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kosuga
authors.forename: Michiko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Tomioka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamashita
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ubara
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Kenmei
authors.initials: K
authors.lastname: Takaichi
authors.forename: Shunya
authors.initials: S
authors.lastname: Uchida
mesh_terms: D000141:Acidosis, Renal Tubular / Q000139:chemically induced* / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000276:immunology*; D024402:Carbonic Anhydrase II / Q000276:immunology*; D004195:Disease Models, Animal; D051379:Mice; D012859:Sjogren's Syndrome / Q000276:immunology*
chemical_list: D000941:Antigens; C035812:renal tubular antigen; D024402:Carbonic Anhydrase II