Induction of anti-carbonic-anhydrase-II antibody causes renal tubular acidosis in a mouse model of Sjogren's syndrome.
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.
Takemoto
Fumi
F
Kidney Center, Toranomon Hospital, Tokyo, Japan. ftakemoto-ind@umin.ac.jp
Katori
Hideyuki
H
Sawa
Naoki
N
Hoshino
Junichi
J
Suwabe
Tatsuya
T
Sogawa
Yoko
Y
Nomura
Kazufumi
K
Nakanishi
Shohei
S
Higa
Yasushi
Y
Kanbayashi
Hiroshi
H
Kosuga
Masahiro
M
Sasaki
Michiko
M
Tomioka
Satoru
S
Yamashita
Masahiro
M
Ubara
Yoshifumi
Y
Yamada
Akira
A
Takaichi
Kenmei
K
Uchida
Shunya
S
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*
D000941:Antigens; C035812:renal tubular antigen; D024402:Carbonic Anhydrase II