Frulloni Luca, Lunardi Claudio, Simone Rita, Dolcino Marzia, Scattolini Chiara, Falconi Massimo, Benini Luigi, Vantini Italo, Corrocher Roberto, Puccetti Antonio
Section of Gastroenterology, University of Verona, Verona, Italy.
N Engl J Med. 2009 Nov 26;361(22):2135-42. doi: 10.1056/NEJMoa0903068.
Autoimmune pancreatitis is characterized by an inflammatory process that leads to organ dysfunction. The cause of the disease is unknown. Its autoimmune origin has been suggested but never proved, and little is known about the pathogenesis of this condition.
To identify pathogenetically relevant autoantigen targets, we screened a random peptide library with pooled IgG obtained from 20 patients with autoimmune pancreatitis. Peptide-specific antibodies were detected in serum specimens obtained from the patients.
Among the detected peptides, peptide AIP(1-7) was recognized by the serum specimens from 18 of 20 patients with autoimmune pancreatitis and by serum specimens from 4 of 40 patients with pancreatic cancer, but not by serum specimens from healthy controls. The peptide showed homology with an amino acid sequence of plasminogen-binding protein (PBP) of Helicobacter pylori and with ubiquitin-protein ligase E3 component n-recognin 2 (UBR2), an enzyme highly expressed in acinar cells of the pancreas. Antibodies against the PBP peptide were detected in 19 of 20 patients with autoimmune pancreatitis (95%) and in 4 of 40 patients with pancreatic cancer (10%). Such reactivity was not detected in patients with alcohol-induced chronic pancreatitis or intraductal papillary mucinous neoplasm. The results were validated in another series of patients with autoimmune pancreatitis or pancreatic cancer: 14 of 15 patients with autoimmune pancreatitis (93%) and 1 of 70 patients with pancreatic cancer (1%) had a positive test for anti-PBP peptide antibodies. When the training and validation groups were combined, the test was positive in 33 of 35 patients with autoimmune pancreatitis (94%) and in 5 of 110 patients with pancreatic cancer (5%).
The antibody that we identified was detected in most patients with autoimmune pancreatitis but also in some patients with pancreatic cancer, making it an imperfect test to distinguish between these two conditions.
自身免疫性胰腺炎的特征是炎症过程导致器官功能障碍。该病病因不明。虽有人提出其自身免疫起源，但从未得到证实，对这种疾病的发病机制也知之甚少。
为了确定与发病机制相关的自身抗原靶点，我们用从20例自身免疫性胰腺炎患者中获得的混合IgG筛选了一个随机肽库。在从患者获得的血清标本中检测到肽特异性抗体。
在检测到的肽中，肽AIP(1-7)被20例自身免疫性胰腺炎患者中的18例血清标本以及40例胰腺癌患者中的4例血清标本识别，但未被健康对照者的血清标本识别。该肽与幽门螺杆菌纤溶酶原结合蛋白（PBP）的氨基酸序列以及泛素蛋白连接酶E3组分n-识别蛋白2（UBR2）具有同源性，UBR2是一种在胰腺腺泡细胞中高度表达的酶。20例自身免疫性胰腺炎患者中有19例（95%）以及40例胰腺癌患者中有4例（10%）检测到针对PBP肽的抗体。在酒精性慢性胰腺炎或导管内乳头状黏液性肿瘤患者中未检测到这种反应性。在另一组自身免疫性胰腺炎或胰腺癌患者中验证了结果：15例自身免疫性胰腺炎患者中有14例（93%）以及70例胰腺癌患者中有1例（1%）抗PBP肽抗体检测呈阳性。当将训练组和验证组合并时，35例自身免疫性胰腺炎患者中有33例（94%）检测呈阳性，110例胰腺癌患者中有5例（5%）检测呈阳性。
我们鉴定出的抗体在大多数自身免疫性胰腺炎患者中被检测到，但在一些胰腺癌患者中也被检测到，这使得它成为区分这两种疾病的不完善检测方法。
