Clinical Cohort Study And Biological Markers Of Autoimmune Pancreatitis

Autoimmune pancreatitis(autoimmune pancreatitis,AIP)is a special type of pancreatitis,which is mediated by autoimmunity mechanism.AIP is a rare disease in the past,due to a variety of clinical manifestations and difficulties in diagnosis,it is often misdiagnosed as a malignant tumor.The epidemiological data on large samples of AIP,clinical diagnosis and treatment,and long-term follow-up were relatively few in China.The mechanism of AIP and the exploration of biomarkers are also urgently needed.The purpose of this study is to establish and summarize a single center AIP clinical data database,extract single central data points for evidence-based medicine analysis,and answer the clinical hot issues.In addition,to explore the new biological markers of AIP and discuss related mechanisms.Part 11.1 Epidemiology and clinical characteristics of type 1 autoimmune pancreatitisObjective:To improve the ability of diagnosis and treatment,a study was carried out to summarize the epidemiological characteristics,clinical manifestations and diagnosis of autoimmune pancreatitis(AIP).Methods:This study retrospectively analyzed the clinical data of all the patients diagnosed with AIP from January 1st 1998 to December 31st 2016 in the ward of Peking union medical college hospital.Results:194 type 1 AIP patients were enrolled in this study.The M/F ratio was 3.51/1,with an average age of 57 ± 15 years.The most common symptom was jaundice,abdominal pain and weight loss.The most common accompanied diseases were sclerosing cholangitis,salivary glands,IgG4 nephropathy.There were 36.68 percent of AIP patients with diabetes mellitus.IgG4,ANA,ESR,c-reactive protein and CA199 were all contribute to disease diagnosis and follow-up.Pathology,PET-CT and steroid therapy response all contributed to the diagnosis of AIP.Conclusions:The incidence of AIP in China is increasing gradually.As a systemic disease,the type 1 AIP has special clinical features and laboratory examination features.1.2 Clinical characters and Experience of diagnosis with treatment of type 2 autoimmune pancreatitis:a retrospective study in a single center Objective:The type 1 autoimmune pancreatitis is gradually being recognized,but the type 2 AIP is still very rare in Asia.This paper summarizes the clinical characters of type-2 AIP patients in Peking union medical college hospital(PUMCH).Methods:From January 2001 to December 2016,all type 2 AIP hospitalized patients who met the ICDC were included in the study.The clinical data,laboratory results and imaging features of all patients were recorded,verified and follow-up.Results:Six patients with type 2 AIP were included in the study.The ratio of men and women was 2/1,with an average age of 38.4 years.67.7%(4/6)patients have UC.37.7%(2/6)of patients were asymptomatic.Three patients were diagnosed by pathology.50%(3/6)of patients showed mass of pancreas,and 50%(3/6)of patients showed pancreatic enlargement.Comparing the type 2 AIP with type 1 AIP,there was a significant difference in the ratio of jaundice and combined inflammatory bowel disease(P<0.01).However,due to the low number of AIP cases,the statistical significance of the differences between age,sex ratio,other clinical symptoms,complications,auxiliary examinations and pathological features was not significant.Conclusions:The clinical manifestations of the type 2 AIP patients in PUMCH are the same as those in foreign countries.1.3 The recurrence rate of AIP its related risk factorsObjective:AIP is an immune-related pancreatic inflammatory disease,and steroid is the first-line treatment regimen with good short-term efficacy.However,the long-term efficacy and prognosis of the steroid therapy AIP are rarely studied.This study aims to study the recurrence rate,relapse related risk factors and steroid related side effects of AIP.Methods:During 1998 to 2016,altogether 149 AIP,who had been followed up for more than 1 year in outpatient,were involved in this study.The clinical data of recurrent groups were analyzed statistically,including independent sample T test,chi-square test,logistics regression and survival table analysis,etc.Results:The recurrence rate of all AIP is about 20.13%.Among all recurrent patients,20%(6/30)had a second recurrence after treatment.The combination of cholangitis and the combination of pancreatic external viscera are high risk factors for secondary recurrence.In the relapse group,the secondary recurrence rate of the immunosuppressive group was lower than the hormone group,but the statistical significance of the difference was not significant(12.5%VS 33.3%,P= 0.194).Long-term side effects of corticosteroids included:2 cases of femoral head necrosis,1 case of bone fracture,and 1 diabetic ketosis.Conclusion:AIP has a recurrence rate of about 20%after cortisone treatment,and the risk factors for secondary recurrence are cholangitis and other organ involvement out of the pancreas.The combined immunosuppressive agent for treatment of AIP steroid therapy can effectively reduce the recurrence rate.1.4 A Case-control and Cohort Study of AutoimmunePancreatitis with Focus on Risk of Colorectal Cancer andPolyposisBackground:The risk of malignancy in autoimmune pancreatitis(AIP)has rarely been reported.With this in mind,we compared the risk of cancer in AIP patients and a control group of alcohol-related chronic pancreatitis(ACP).Methods:In a single center,retrospective cohort study,we collected AIP patients data who were admitted between Januarylst 1998 and September 31st 2016.Eligible ACP patients diagnosed during 1985 and 2010 were recruited as control group.Results:A total of 199 AIP patients including 194 cases of type 1,and 5 cases of type 2.175 AIP which are regularly followed up together with 127 ACP controls were included in this study.Of the 199 AIP patients,12 patients were found with malignancy(6.86%),while 2 patients out of 127(1.57%)ACP patients were found with cancer.The occurrence rates of malignant tumors were statistically higher in AIP patients than ACP controls(P<0.001.More specifically,6(50%)out of 12 cancers were colorectal cancers in AIP group.Likewise,the rate of colonic polyps in the AIP patients was 7.04%,which was significantly higher than 0.79%in ACP.Moreover,immunoperoxidase stain for IgG4 in AIP patients with colonic adenoma or colorectal carcinoma revealed diffuse and marked infiltration of IgG4 positive plasma cells.Conclusions:Patients with AIP were at high risk of developing various tumors,especially the colorectal cancer and colorectal polyps.Clinicians may need to consider early colonoscopy scan for AIP patients.Part 2A preliminary study on the application of plasma miRNA in AIP diagnosis and prognosis and related possible mechanisms Objective:To explore the expression and possible roles of miRNA in exosome vesicles(EV)and peripheral blood mononuclear cells(PBMC)in AIP patients.Methods:1.Through clinical screening,this study involved 3 groups include autoimmune pancreatitis,chronic pancreatitis and health control groups.The AIP group was treated with standard regimen steroid therapy.The comparison of serology and imaging was made before and after steroid treatment.2.Peripheral blood samples were taken from each patient.The plasma exosome vesicles and the peripheral blood mononuclear cell were isolated separately.3.The miRNA in plasma and EV were extracted,and the second-generation gene sequencing library was carried out after the quality inspection.The miRNA was selected and the target miRNA was initially screened by logical and statistical analysis,4.Using selected miRNA for target gene prediction,and searching the correlation pathway and regulation network through biological database.Results:1.The E V in the peripheral blood of AIP has stable measurement.2.MiRNA of EV and PBMC in peripheral blood had significant difference expression among AIP,CP and healthy control,especially in AIP before and after steroid treatment group.The number and expression amount of miRNA in exocrine were higher than that of PBMC.3.Using the second-generation sequencing technology,we preliminarily founded 47 differentially expressed miRNAs including hsa-mir-3656,which laid the foundation for further searching for the biomarkers of AIP and revealing the pathogenesis of AIP.4.With the enrichment analysis of the KEGG pathway of miRNA target gene,MAPK signaling pathway may be involved in AIP response to hormone and occupy an important position.Conclusion:The detection of miRNA in EV may be an effective way to find the biomarkers of AIP.