Analysis of Humoral Immune Response in Experimental Autoimmune Pancreatitis in Mice
Analysis of Humoral Immune Response in Experimental Autoimmune Pancreatitis in Mice
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DOI：
10.1097/mpa.0b013e3181bab5e2
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发表时间：
2010-03-01
期刊：
影响因子：
2.9
通讯作者：
Chiba, Tsutomu
中科院分区：
文献类型：
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作者：
Asada, Masanori;Nishio, Akiyoshi;Chiba, Tsutomu
目的：研究自发性胰腺外分泌性胰腺炎的MRL/MP小鼠的自身免疫反应。方法：6周龄雌性小鼠以5 mg/kg体重每周2次腹腔注射多聚肌胞苷多胞苷，连续12周。这些小鼠被连续处死，并用组织学评分系统对它们的胰腺炎严重程度进行分级。结果：多聚肌苷多胞酸可加速胰腺炎的发展，B220(+)B细胞和CD138(+)浆细胞大量浸润。检测到多种针对自身抗原的自身抗体，包括碳酸氢酶II和乳铁蛋白，但没有检测到针对谷氨酸脱羧酶的自身抗体。其中，针对胰腺分泌性胰蛋白酶抑制物(PSTI；91.7%)的自身抗体比针对碳酸氢酶II(33.3%)或乳铁蛋白(45.8%)的自身抗体更普遍。抗PSTI抗体表位的测定表明，大部分免疫反应针对PSTI上抑制胰酶活性的活性部位。结论：PSTI蛋白的自身免疫应答可能导致PSTI活性失效，导致胰酶原激活，从而导致疾病进展。
Objectives: To study the autoimmune response in MRL/Mp mice, which spontaneously develop pancreatitis in the exocrine pancreatic tissue.Methods: Six-week-old female mice were injected intraperitoneally with polyinosinic polycytidylic acid at a dose of 5 mg/kg of body weight twice a week for up to 12 weeks. The mice were serially killed, and the severity of their pancreatitis was graded with a histological scoring system. Immunohistological examinations were performed, and the serum levels of autoantibodies were measured by enzyme-linked immunosorbent assay.Results: The administration of polyinosinic polycytidylic acid accelerated the development of pancreatitis, with abundant infiltration of B220(+) B cells and CD138(+) plasmacytes. Various autoantibodies directed against autoantigens, including carbonic anhydrase II and lactoferrin, were detected but none against glutamic acid decarboxylase. Of these, autoantibodies directed against the pancreatic secretory trypsin inhibitor (PSTI; 91.7%) were more prevalent than those against carbonic anhydrase II (33.3%) or lactoferrin (45.8%). Determination of the epitope of the anti-PSTI antibody showed that most immunoreactivity was directed at the site on PSTI that is active in the suppression of trypsin activity.Conclusions: The autoimmune response to PSTI protein may induce a failure of PSTI activity, resulting in the activation of trypsinogen and the subsequent disease progression.