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Vol.53 (2007) >

Please use this identifier to cite or link to this item: http://ir.fmu.ac.jp/dspace/handle/123456789/214

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Title: Breakthrough of immune self-tolerance to calreticulin induced by CpG-oligodeoxynucleotides as adjuvant
Other Titles: Breakthrough of tolerance to calreticulin
Authors: Abe, Kazumichi
Ohira, Hiromasa
Kobayashi, Hiroko
Saito, Hironobu
Takahashi, Atsushi
Rai, Tsuyoshi
Kanno, Yukiko
Monoe, Kyoko
Watanabe, Hiroshi
Irisawa, Atsushi
Sato, Yukio
Affiliation: 内科学第二講座
大学健康管理センター
Source title: Fukushima Journal of Medical Science
Volume: 53
Issue: 2
Start page: 95
End page: 108
Issue Date: Dec-2007
Abstract: Reportedly, bacterial DNA containing unmethylated cytosine-guanosine dinucleotide motif-containing oligodeoxynucleotides (CpG-ODNs) can induce Th1-type adjuvant effects. We produced autoantibodies and induced hepatitis in mice using extracted proteins from human hepatocytes with CpG-ODNs as adjuvant. Western blot analysis was performed of sera from immunized mice and two patients with autoimmune hepatitis (AIH). When a common band was detected, N-terminal amino acid sequencing was performed to determine its site. For detection of antibodies against the identified protein (calreticulin), ELISA was performed of sera of 50 patients with AIH: 45 with primary biliary cirrhosis (PBC), 24 with chronic hepatitis C (CH), and 24 healthy controls. Mice were immunized with calreticulin protein with CpG-ODNs as adjuvant. Several reacted bands were detected in their sera; in addition, a common band to the sera of patients with AIH was detected at 60 kDa. Subsequent N-terminal amino acid sequencing revealed that the protein was human calreticulin. ELISA showed that, of patients with AIH, PBC, and CH, 30.0% (15/50), 17.8% (8/45), and 12.5% (3/24), respectively, were positive for anti calreticulin antibodies. Splenocytes from immunized mice produced IFN-gamma after they were pulsed with calreticulin protein. Histological analyses of liver specimens taken from mice immunized with calreticulin protein together with CpG-ODNs showed spotty and focal necrosis. Immunofluorescence analysis showed increased expression of calreticulin in the liver treated with CpG-ODNs. These results suggest that a breakthrough of immune self tolerance to calreticulin is induced with CpG-ODNs as adjuvant and that calreticulin protein might be a target antigen in this model.
Publisher: The Fukushima Society of Medical Science
Publisher (Alternative foam): 福島医学会
language: eng
URI: http://ir.fmu.ac.jp/dspace/handle/123456789/214
Full text URL: http://ir.fmu.ac.jp/dspace/bitstream/123456789/214/1/FksmJMedSci_53_p95.pdf
ISSN: 0016-2590
PubMed ID: 18402289
Rights: © 2007 The Fukushima Society of Medical Science
Appears in Collections:Vol.53 (2007)

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