The Clinical Study of IgG4 Associate Pancreatitis (Autoimmune Pancreatitis) and Development of its Diagnostic System

目前的研究显示，自身免疫性胰腺炎的特点是老年男性优势和梗阻性黄疸为初始症状。有时临床上难以与胰腺癌鉴别，但血清IgG4测定是鉴别的有效工具。随访胰脏图变化明显，显示本病临床特征的多样性。本病原发自身抗体如SS-A、SS-B和抗线粒体抗体阳性率低。我们在自身免疫性胰腺炎合并硬化性胆管炎患者的血清中发现了抗α -fodrin抗体，提示该抗体与这种胰腺外病变的形成有关。自身免疫性胰腺炎的特点是多种胰腺外病变同时发生。本研究显示肝门病变和腹膜后纤维化，提示本病可视为全身性疾病，如多灶性纤维硬化。自身免疫性胰腺炎与HLA DRB1*0405-DQB1*0401单倍型显著相关，该单倍型可能向T细胞呈递特异性抗原肽，引发自身免疫反应。本研究发现，本病患者血清对25 kDa带有特异性反应，后证实为超氧化物歧化酶2 （SOD2）。在许多自身免疫性疾病中，自身抗体对SOD2起反应，提示目标抗原的候选。然而，重组SOD2蛋白不能与患者血清发生反应。我们需要进一步研究以确定该蛋白的葡萄糖偶联部分是否为抗原决定物。

The present study revealed that autoimmune pancreatitis is characterized by elderly male preponderance and obstructive jaundics as an initial symptome. Sometimed it is difficult to differentiate this disease from pancreatic cancer clinically, but serum IgG4 measurement is useful tool for differentiation. Significant changes of pancreatigram in follow-up study showed the diversity of clinical features of this disease. We found low frequency of authentic autoantibodies, such as SS-A, SS-B and anti-mitochondrial antibody in this disease. We found anti-alfa-fodrin antibody in sera of autoimmune pancreatitis patients with sclerosing cholangitis, suggesting that this antibody is associated the formation of such an extra-pancreatic lesion.Auotimmune pancreatitis is characterized by co-occurrence of various exta-pancreatic lesions._The present study showed hilar lesions by gallium-67 scintigrphy and retroperitoneal fibrosis, suggesting that this disease is regarded as systemic disease, such as multifocal fibrosclerosis. The autoimmune pancreatitis is significantly associated with HLA DRB1*0405-DQB1*0401 haplotype, which may present specific antigen peptide to T cells, resulting in the initiation of autoi, mmune response.The present study revealed that sera of the patient with this disease react specifically to 25 kDa band, which was later confirmed as superoxide dismutase 2 (SOD2). In many autoimmune diseases, autoantibodies react to SOD2, suggesting the candidate of target antigen. However, recombinant SOD2 protein could not react with patient sera. We should perform further study to confirm whether glucoconjugate portion of this protein is antigen determinant.