Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Autoimmune pancreatitis:Cornerstones and future perspectives

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and fibrosis.Although AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic diseases.AIP is commonly classified into two types.Type 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel diseases.Additionally,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical literature.The clinical manifestations of AIP mainly include painless jaundice and weight loss.Elevated serum IgG4 levels are particularly characteristic of AIP-1.Diagnosis relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic disorders.The mainstay of treatment for AIP is steroid therapy,which is effective in most cases.Severe cases might require additional imm-unosuppressive agents.This review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment options.We also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al.The authors identified higher serum immunoglobulin(Ig)G4 levels and age over 55 years as independent risk factors for disease relapse.Despite notable strengths,it is crucial to address potential biases.Firstly,the cohort study included 189 patients with autoimmune pancreatitis(AIP)type 1(with higher IgG4 seropositivity and higher relapse)and 24 with type 2(with lower IgG4 seropositivity and lower relapse).Consequently,most,if not all,AIP type 2 patients were assigned to the normal group,possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse.Secondly,the authors did not provide sufficient details regarding AIP diagnosis,such as the ratio of definitive vs probable cases and the proportion of biopsies.In cases where histological evidence is unavailable or indeterminate,AIP type 2 may be misdiagnosed as definitive type 1,and type 1 may also be misdiagnosed as probable type 2,particularly in cases with normal or mildly elevated serum IgG4 levels.Lastly,in this retrospective study,approximately one-third of the consecutive patients initially collected were excluded for various reasons.Accordingly,the impact of nonrandom exclusion on relapse outcomes should be carefully considered.In conclusion,the paper by Zhou et al offers plausible,though not entirely compelling,evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse.The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping,heavily dependent on obtaining histological specimens.In this regard,endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process,contributing to mitigating biases in future explorations of the disease.

Unmet needs in biomarkers for autoimmune pancreatitis diagnosis

Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.

Understanding autoimmune pancreatitis: Clinical features, management challenges, and association with malignancies

In this editorial we comment on the article by Jaber et al.Autoimmune pancreatitis(AIP)represents a distinct form of pancreatitis,categorized into AIP-1 and AIP-2,characterized by obstructive jaundice,lymphoplasmacytic infiltrate,and fibrosis.AIP-1,associated with elevated immunoglobulin G4(IgG4)levels,exhibits higher relapse rates,affecting older males,while AIP-2 is less common and linked to inflammatory bowel disease.AIP is considered a manifestation of IgG4-related systemic disease,sharing characteristic histological findings.Steroids are the primary treatment,with emerging biomarkers like interferon alpha and inter-leukin-33.AIP poses an increased risk of various malignancies,and the assoc-iation with pancreatic cancer is debated.Surgery is reserved for severe cases,necessitating careful evaluation due to diagnostic challenges.AIP patients may have concurrent PanINs but display favorable long-term outcomes compared to pancreatic cancer patients.Thorough diagnostic assessment,including biopsy and steroid response,is crucial for informed surgical decisions in AIP.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated surgi-cally.We studied the diagnosis and treatment of a patient with type 1 AIP recent-ly admitted to our hospital,and reviewed the literature to provide a reference for clinical diagnosis of AIP.CASE SUMMARY The chief complaint was yellowing of the body,eyes and urine for 21 d.The pa-tient's clinical presentation was obstructive jaundice and imaging suggested pan-creatic swelling.It was difficult to distinguish between inflammation and tumor.Serum immunoglobulin G4(IgG4)was markedly elevated.IgG4 is an important serological marker for type 1 AIP.The patient was diagnosed with AIP,IgG4-related cholangitis,acute cholecystitis and hepatic impairment.After applying hormonal therapy,the patient's symptoms improved significantly.At the same time,imaging suggested that pancreatic swelling subsided,and liver function and other biochemical indicators decreased.The treatment was effective.CONCLUSION In patients with pancreatic swelling,the possibility of AIP should be considered.

Glucocorticoid therapy in pancreatic portal hypertension associated with autoimmune pancreatitis:A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct.Some studies have reported that AIP can cause hemorrhage of gastric varices(GV)related to portal hypertension(PH).However,such cases are rare.In addition,the association of PH with AIP is unclear.At the same time,the efficacy and duration of glucocorticoid therapy is also controversial.CASE SUMMARY In this case,we reported a case of GV in pancreatic PH associated with AIP.Enhanced abdominal computed tomography(CT)suggested splenic vein(SV)and superior mesenteric vein(SMV)thromboses.The patient received a long-term glucocorticoid therapy,that the initial dose of 40 mg is reduced weekly by 5 mg,and then reduced to 5 mg for long-term maintenance.CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized,pancreatic stiffness and swelling were ameliorated,and the GV almost completely disappeared.CONCLUSION Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.

Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level:A single-center,retrospective cohort study

BACKGROUND Autoimmune pancreatitis(AIP)has been linked with elevated immunoglobulin(Ig)G4 levels.The characteristics and outcomes of AIP based on serum markers have not been fully evaluated.AIM To compare clinical features,treatment efficacy,and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse.METHODS A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021.According to the serum IgG4 level,all patients were divided into two groups,the abnormal group(n=148)with a high level of IgG4[>2×upper limit of normal(ULN)]and the normal group(n=65).The t-test or Mann-Whitney U test was used to compare continuous variables.Categorical parameters were compared by theχ^(2) test or Fisher’s exact test.Kaplan-Meier curves Zhou GZ et al.Clinical characteristics and outcome of AIP WJG https://www.wjgnet.com 5126 September 21,2023 Volume 29 Issue 35 and log-rank tests were established to assess the cumulative relapse rates.Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse.RESULTS Compared with the normal group,the abnormal group had a higher average male age(60.3±10.4 vs 56.5±12.9 years,P=0.047);higher level of serum total protein(72.5±7.9 g/L vs 67.2±7.5 g/L,P<0.001),IgG4(1420.5±1110.9 mg/dL vs 252.7±106.6 mg/dL,P<0.001),and IgE(635.6±958.1 IU/mL vs 231.7±352.5 IU/mL,P=0.002);and a lower level of serum complement C3(100.6±36.2 mg/dL vs 119.0±45.7 mg/dL,P=0.050).In addition,a lower number of cases with abnormal pancreatic duct and pancreatic atrophy(23.6%vs 37.9%,P=0.045;1.6%vs 8.6%,P=0.020,respectively)and a higher rate of relapse(17.6%vs 6.2%,P=0.030)were seen in the abnormal group.Multivariate analyses revealed that serum IgG4[(>2×ULN),hazard ratio(HR):3.583;95%confidence interval(CI):1.218–10.545;P=0.020]and IgA(>1×ULN;HR:5.908;95%CI:1.199–29.120;P=0.029)and age>55 years(HR:2.383;95%CI:1.056–5.378;P=0.036)were independent risk factors of relapse.CONCLUSION AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate.Several factors,such as IgG4 and IgA,are associated with relapse.

Serum biomarkers for the differentiation of autoimmune pancreatitis from pancreatic ductal adenocarcinoma

Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).Serum biomarkers,substances that quantitatively change in sera during disease development,are a promising non-invasive tool with high utility for differentiating between these diseases.In this way,the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4(IgG4)antibody are elevated.However,this approach has some drawbacks.Notably,IgG4 antibody concentrations are also elevated in sera from some patients with PDAC.This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC,evaluating the usefulness of immunoglobulins,autoantibodies,chemokines,and cytokines.The proposed serum biomarkers have proven useful,although most studies had a small sample size,did not examine their presence in patients with PDAC,or did not test them in humans.In addition,current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity,either alone or in combination with clinical data and/or radiological images.

Clinical characteristics and outcomes of autoimmune pancreatitis based on serum immunoglobulin G4 levels:A single-center,retrospective cohort study

Autoimmune pancreatitis(AIP)is a complex,poorly understood disease gaining increasing attention."Clinical Characteristics and Outcome of AIP Based on Serum IgG4 levels,"investigated AIP with a focus on serum immunoglobulin(Ig)G4 levels.The 213 patients with AIP were classified according to serum IgG4 levels:Abnormal(elevated)and normal.Patients with higher IgG4 levels exhibited a more active immune system and increased relapse rates.Beyond IgG4,the IgA levels and age independently contributed to relapse risk,guiding risk assessment and tailored treatments for better outcomes.However,limitations persist,such as no IgA correlation with IgG4 levels,absent data on autoantibodypositive AIP cases critical for Asian diagnostic criteria,and unexplored relapse rates in high serum IgG AIP by subtype.Genetic factors and family histories were not addressed.As the understanding and referral of seronegative AIPs increase,there's a growing need for commercially available,highly sensitive,and specific autoantibodies to aid in diagnosing individuals with low or absent serum IgG4 levels.

Challenges for clinicians treating autoimmune pancreatitis:Current perspectives

Autoimmune pancreatitis(AIP)is a rare disease clinically characterized by obstructive jaundice,unintentional weight loss,acute pancreatitis,focal pancreatic mass,and diabetes.AIP is classified into two subtypes-type 1 and type 2-according to pathological findings,clinical features,and serology test results,but some cases may be defined as type not otherwise in the absence of pathological findings and inflammatory bowel disease.To address the differences in diagnostic criteria by country,standard diagnostic criteria for AIP were proposed in 2011 by an international consensus of expert opinions.Differential diagnosis of AIP from pancreatic ductal adenocarcinoma is important but remains challenging for clinicians.Fortunately,all subtypes of AIP show dramatic response to steroid treatment.This review discusses the current perspectives on the diagnosis and management of AIP in clinical practice.

Autoimmune pancreatitis in the context of IgG4-related disease:Review of imaging findings

Current understanding of autoimmune pancreatitis (AIP) recognizes a histopathological subtype of the disease to fall within the spectrum of IgG4-related disease. Along with clinical, laboratory, and histopathological data, imaging plays an important role in the diagnosis and management of AIP, and more broadly, within the spectrum of IgG4-related disease. In addition to the defined role of imaging in consensus diagnostic protocols, an array of imaging modalities can provide complementary data to address specific clinical concerns. These include contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging for pancreatic parenchymal lesion localization and characterization, endoscopic retrograde and magnetic resonance cholangiopancreatography (ERCP and MRCP) to assess for duct involvement, and more recently, positron emission tomography (PET) imaging to assess for extra-pancreatic sites of involvement. While the imaging appearance of AIP varies widely, certain imaging features are more likely to represent AIP than alternate diagnoses, such as pancreatic cancer. While nonspecific, imaging findings which favor a diagnosis of AIP rather than pancreatic cancer include: delayed enhancement of affected pancreas, mild dilatation of the main pancreatic duct over a long segment, the &#x0201c;capsule&#x0201d; and &#x0201c;penetrating duct&#x0201d; signs, and responsiveness to corticosteroid therapy. Systemic, extra-pancreatic sites of involvement are also often seen in AIP and IgG4-related disease, and typically respond to corticosteroid therapy. Imaging by CT, MR, and PET also play a role in the diagnosis and monitoring after treatment of involved sites.

Diagnosis and management of autoimmune pancreatitis:Experience from China

AIM： To determine the clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities in patients with autoimmune pancreatitis （AIP）. METHODS： In this retrospective study, the data of patients with diagnosed chronic pancreatitis （CP） between 1995 and 2006 in Chinese PLA General Hospital were included to screen for the cases with AIP, according to the following diagnostic criteria： （1） diagnostic histopathologic features, and abound IgG4-positive plasma cells on pancreatic tissues; （2） characteristic imaging on computed tomography and pancreatography, together with increased serum IgG, y-globulin levels or presence of autoantibodies; （3） response to steroid therapy. The clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities, and outcome of AIP cases were reviewed. RESULTS： Twenty-five （22 male, 3 female; mean age 54 years, 36-76 years） out of 510 CP patients were diagnosed as AIP, which accounted for 49% （21/43） of CP population undergoing surgical treatment in the same period. The main clinical manifestations included intermittent or progressive jaundice in 18 cases （72%）, abdominal pain in 11 （44%）, weight loss in 10 （40%）, and 3 cases had no symptoms. The imaging features consisted of pancreatic enlargement, especially in the head of pancreas （18 cases）, strictures of main pancreatic duct and intrapancreatic bile duct. Massive lymphocytes and plasma cells infiltration in pancreatic tissues were showed on pathology, as well as parenchymal fibrosis. Twenty-three patients were misdiagnosed as pancreaticobiliary malignancy, and 21 patients underwent exploratory laparotomy, theremaining 4 patients dramatically responded to steroid therapy. No pancreatic cancer occurred during a mean 46-mo follow-up period. CONCLUSION： AIP patients always are subjected to mistaken diagnosis of pancreatic cancer and an unnecessary surgical exploration, due to its similarity in clinical features with pancreatic cancer. The differential diagnosis with high index of suspicion of AIP would improve the diagnostic accuracy for AIR

Diagnostic criteria for autoimmune pancreatitis in Japan

Autoimmune pancreatitis （AIP） is a particular type of pancreatitis of presumed autoimmune etiology. Currently, AIP should be diagnosed based on combination of clinical, serological, morphological, and histopathological features. When diagnosing AIP, it is most important to differentiate it from pancreatic cancer. Diagnostic criteria for AIP, proposed by the Japan Pancreas Society in 2002 first in the world, were revised in 2006. The criteria are based on the minimum consensus of AIP and aim to avoid misdiagnosing pancreatic cancer as far as possible, but not for screening AIR The criteria consist of the following radiological, serological, and histopathological items： （1） radiological imaging showing narrowing of the main pancreatic duct and enlargement of the pancreas, which are characteristic of the disease; （2） laboratory data showing abnormally elevated levels of serum y-globulin, IgG or IgG4, or the presence of autoantibodies; （3） histopathological examination of the pancreas demonstrating marked fibrosis and prominent infiltration of lymphocytes and plasma cells, which is called lymphoplasmacytic sclerosing pancreatitis （LPSP）. For a diagnosis of AIP, criterion 1 must be present, together with criterion 2 and/ or criterion 3. However, it is necessary to exclude malignant diseases such as pancreatic or biliary cancer.

Autoimmune pancreatitis:Multimodality non-invasive imaging diagnosis

Autoimmune pancreatitis (AIP) is characterized by obstructive jaundice, a dramatic clinical response to steroids and pathologically by a lymphoplasmacytic infiltrate, with or without a pancreatic mass. Type 1 AIP is the pancreatic manifestation of an IgG4-related systemic disease and is characterized by elevated IgG4 serum levels, infiltration of IgG4-positive plasma cells and extrapancreatic lesions. Type 2 AIP usually has none or very few IgG4-positive plasma cells, no serum IgG4 elevation and appears to be a pancreas-specific disorder without extrapancreatic involvement. AIP is diagnosed in approximately 2%-6% of patients that undergo pancreatic resection for suspected pancreatic cancer. There are three patterns of autoimmune pancreatitis: diffuse disease is the most common type, with a diffuse, &#x0201c;sausage-like&#x0201d; pancreatic enlargement with sharp margins and loss of the lobular contours; focal disease is less common and manifests as a focal mass, often within the pancreatic head, mimicking a pancreatic malignancy. Multifocal involvement can also occur. In this paper we describe the features of AIP at ultrasonography, computed tomography, magnetic resonance and positron emission tomography/computed tomography imaging, focusing on diagnosis and differential diagnosis with pancreatic ductal adenocarcinoma. It is of utmost importance to make an early correct differential diagnosis between these two diseases in order to identify the optimal therapeutic strategy and to avoid unnecessary laparotomy or pancreatic resection in AIP patients. Non-invasive imaging plays also an important role in therapy monitoring, in follow-up and in early identification of disease recurrence.

Diagnosis of autoimmune pancreatitis

Autoimmune pancreatitis(AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to Ig G4(lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion(idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum Ig G4 and positive serum autoantibodies, abundant infiltration of Ig G4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology(IAP).

Strategy to differentiate autoimmune pancreatitis from pancreas cancer

Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include:fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed en- hancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.

MRCP and MRI findings in 9 patients with autoimmune pancreatitis

AIM： To evaluate magnetic resonance cholangiopancreatography （HRCP） findings in conjunction with magnetic resonance （MR） images in autoimmune pancreatitis （AIP） patients. METHODS： Nine patients with AIP underwent HRI, HRCP, endoscopic retrograde cholangiopancreatography （ERCP）, computed tomography, and ultrasonography. The HRCP and MR images taken before and after steroid therapy were reviewed and compared with other imaging modalities. The HRCP findings of the AIP cases were compared to those of 10 cases with carcinoma of the head of the pancreas.RESULTS： On MRCP, the narrowed portion of the main pancreatic duct noted on ERCP was not visualized, while the non-involved segments of the main pancreatic duct were visualized. The degree of upstream dilatation of the proximal main pancreatic duct was milder than that seen in cases of pancreatic carcinoma. Stenosis or obstruction of the lower bile duct was detected in 8 patients. MR images showed enlargement of the pancreas with decreased signal intensity on T1- weighted MR images, increased signal intensity on T2- weighted MR images, and, in 3 patients, a hypointense capsule-like rim. After steroid therapy, the previously not visualized portion of the main pancreatic duct was seen, along with improvement of the bile duct stenosis. Pancreatic enlargement decreased, and the abnormal signal intensity on both T1- and T2-weighted MR images became isointense.CONCLUSION： MRCP cannot differentiate irregular narrowing of the main pancreatic duct seen with AIP from stenosis of the main pancreatic duct seen with pancreatic carcinoma. However, MRCP findings in conjunction with MR imaging of pancreatic enlargement that shows abnormal signal intensity on T1- and T2- weighted MR images are useful in supporting a diagnosis of AIP.

Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis:A prospective study using IgG4-immunostaining

AIM： TO examine the histological and immunohistochemical findings of biopsy specimens taken from the major duodenal papilla of autoimmune pancreatitis （AIP） patients. METHODS： The major duodenal papilla in the resected pancreas of 3 patients with AIP and of 5 control patients [pancreatic carcinoma （n = 3） and chronic alcoholic pancreatitis （17 = 2）] was immunostained using anti-CD4-T cell, CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major duodenal papilla of 2 patients with AIP and 5 control patients with suspected papillitis were prospectively taken during duodenoscopy and immunohistochemically examined. RESULTS： Moderate or severe Iymphoplasmacytic in- filtration including many CD4-positive or CD8-positive T lymphocytes and IgG4-positive plasma cells （≥10/HPF）, was observed in the major duodenal papilla of all 3 patients with AIR The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with/kiP, but in controls, there were only a few （≤3/HPF） IgG4-positive plasma cells infiltrating the major duodenal papilla. CONCLUSIONS： An abundant infiltration of IgG4-positive plasma cells is specifically detected in the major duodenal papilla of patients with A/P. Although this is a preliminary study, IgG4-immunostaining of biopsy specimens taken from the major duodenal papilla may support the diagnosis of AIR

Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Solitary organ autoimmune disorders,formerly known as autoimmune pancreatitis(AIP),autoimmune sialadenitis,and autoimmune sclerosing cholangitis,are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease(IgG4-RD).AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody(Ab),accumulation of IgG4-expressing plasmacytes in the affected organs,and involvement of multiple organs.It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity.However,a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype.In addition,disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone.Therefore,it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD.Recently,we found that activation of plasmacytoid dendritic cells producing both interferon-α(IFN-α)and interleukin-33(IL-33)mediate murine AIP and human IgG4-RD.More importantly,we provided evidence that serum concentrations of IFN-αand IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders.In this Frontier article,we have summarized and discussed biomarkers of AIP and IgG4-RD,including Igs,autoAbs,and cytokines to provide useful information not only for clinicians but also for researchers.