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 (n = 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 lymphoplasmacytic infiltration 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 AIP. The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with AIP, 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 AIP. Although this is a preliminary study, IgG4-immunostaining of biopsy specimens taken from the major duodenal papilla may support the diagnosis of AIP.     

Hypothyroidism in patients with autoimmune pancreatitis

AIM To examine thyroid function and clinical features of hypothyroidism in autoimmune pancreatitis(AIP) patients.METHODS We examined thyroid function in 77 patients with type 1 AIP(50 males, 27 females; median age 68 years, range 33-85) diagnosed according to the Japanese diagnostic criteria for AIP 2011. We compared clinical and serological findings between patients with and without various categories of hypothyroidism. The change in hypothyroidism after steroid therapy was also examined. RESULTS Eight patients(10%) had hypothyroidism of 6 patients had subclinical hypothyroidism with a normal serum free thyroxine(FT4) and high thyroid stimulating hormone(TSH) level, and 2 patients had central hypothyroidism with low serum free triiodothyronine(FT3), FT4 and TSH levels. A significant goiter of the thyroid was not observed in any patient. There were no significant differences in age; male to female ratio; serum concentrations of IgG and IgG 4-related disease(IgG4-RD); presence of antithyroglobulin antibody, antinuclear antigen or rheumatoid factor; or presence of extrapancreatic lesions between the 6 patients with subclinical hypothyroidism and patients with euthyroidism. After steroid therapy, both subclinical and central hypothyroidism improved with improvement of the AIP.CONCLUSION Hypothyroidism was observed in 8(10%) of 77 AIP patients and was subclinical in 6 patients and central in 2 patients. Further studies are necessary to clarify whether this subclinical hypothyroidism is another manifestation of IgG4-RD.     

Immunoglobulin G4-related pancreatic and biliary diseases

BACKGROUND:

Autoimmune pancreatitis and autoimmune cholangitis are new clinical entities that are now recognized as the pancreaticobiliary manifestations of immunoglobulin (Ig) G4-related disease.

OBJECTIVE:

To summarize important clinical aspects of IgG4-related pancreatic and biliary diseases, and to review the role of IgG4 in the diagnosis of autoimmune pancreatitis (AIP) and autoimmune cholangitis (AIC).

METHODS:

A narrative review was performed using the PubMed database and the following keywords: “IgG4”, “IgG4 related disease”, “autoimmune pancreatitis”, “sclerosing cholangitis” and “autoimmune cholangitis”. A total of 955 articles were retrieved; of these, 381 contained relevant data regarding the IgG4 molecule, pathogenesis of IgG-related diseases, and diagnosis, management and long-term follow-up for patients with AIP and AIC. Of these 381 articles, 66 of the most pertinent were selected.

RESULTS:

The selected studies demonstrated the increasing clinical importance of both AIP and AIC, which can mimic pancreatic cancer and cholangiocarcinoma, respectively. IgG4 titration in tissue or blood cannot be used alone to diagnose all IgG4-related diseases; however, it is often a useful adjunct to clinical, radiological and histological features. AIP and AIC respond to steroids; however, relapse is common and long-term maintenance treatment often required.

CONCLUSIONS:

A review of the diagnosis and management of both AIC and AIP is timely and pertinent to clinical practice because the amount of information regarding these conditions has increased substantially in the past few years, resulting in significant impact on the clinical management of affected patients.     

Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis: A prospective study using TgG4-immunostaining

AIM: To examine the histological and immunohistochemical findings of biopsy specimens taken from the major duodenal papilla of autoirnrnune 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 (n = 2)] was irnrnunostained using anti-CD4-T cell, CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major duodenal papilla of 2patients with AIP and 5 control patients with suspected papillitis were prospectively taken during duodenoscopy and immunohistochernically examined.RESULTS: Moderate or severe lyrnphoplasrnacytic infiltration 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 AIP. The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with AIP, 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 AIP. Although this is a preliminary study, IgG4-irnmunostaining of biopsy specimens taken from the major duodenal papilla may support the diagnosis of AIP.     

A comparison of the diagnostic efficacy in type 1 autoimmune pancreatitis based on biopsy specimens from various organs

BackgroundComprehensive immunostaining evaluation of the biopsy specimens from various organs with type 1 autoimmune pancreatitis (AIP) has not been elucidated. Our aim was to clarify which of these biopsy specimens and counting method could be a useful tool for supporting the diagnosis of AIP.MethodsWe retrospectively evaluated biopsy specimens from pancreas (n = 19), stomach (n = 28), duodenum (n = 27), duodenal papilla (n = 25), colon (n = 19), liver (n = 11), bile duct (n = 24), and minor salivary gland (n = 13) in 36 patients with AIP. Positive IgG4 immunostaining (>10 plasma cells/high-power field [HPF]) and positive IgG4/IgG ratio (>40%) of biopsy specimens from 8 sites of 6 organs in one HPF and an average from 3 HPFs were compared between AIP and controls.ResultsThe sensitivity of IgG4 immunostaining for AIP in one HPF were 16% in pancreas, 14% in stomach, 15% in duodenum, 52% in duodenal papilla, 11% in colon, 27% in liver, 21% in bile duct and 8% in minor salivary gland, respectively. The positive IgG4 immunostaining of the duodenal papilla in one HPF showed the highest sensitivity (52%) and accuracy (73%) among the 8 sites. It also showed the highest sensitivity among 4 different counting methods (IgG4 immunostaining in one HPF and 3 HPFs, both IgG4 immunostaining and IgG/IgG4 ratio in one HPF and 3 HPFs), but there were no significant differences with respect to specificity and accuracy.ConclusionsIgG4 immunostaining of swollen duodenal papilla with more than 10 IgG4-positive plasma cells in at least one HPF is useful for supporting the diagnosis of AIP.     

Sclerosing cholangitis associated with autoimmune pancreatitis differs from primary sclerosing cholangitis

AIM： To clarify the characteristic features of biliary lesions in patients with autoimmune pancreatitis （AIP） and compare them with those of primary sclerosing cholangitis （PSC）.METHODS： The clinicopathological characteristics of 34 patients with sclerosing cholangitis （SC） associated with AIP were compared with those of 4 patients with PSC.RESULTS： SC with AIP occurred predominantly in elderly men. Obstructive jaundice was the most frequent initial symptom in SC with AIP. Only SC patients with AIP had elevated serum IgG4 levels, and sclerosing diseases were more frequent in these patients. SC patients with AIP responded well to steroid therapy. Segmental stenosis of the lower bile duct was observed only in SC patients with AIP, but a beaded and prunedtree appearance was detected only in PSC patients.Dense infiltration of IgG4-positive plasma cells was detected in the bile duct wall and the periportal area, as well as in the pancreas, of SC patients with AIP.CONCLUSION： SC with AIP is distinctly different from PSC. The two diseases can be discriminated based on cholangiopancreatographic findings and serum IgG4 levels.     

Identification and characterization of IgG4‐associated autoimmune hepatitis

Background: Autoimmune hepatitis (AIH) and autoimmune pancreatitis (AIP) share clinical and pathological features such as high serum levels of immunoglobulin (Ig) G and autoantibodies, and lymphoplasmacytic infiltration, suggesting the presence of common immunological abnormalities. However, little is known about the possible involvement of IgG4, a hallmark of AIP, in AIH. Aims: In this study, we examined whether the IgG4 response contributes to the histopathological and clinical findings in AIH. Methods: Liver sections from 26 patients with AIH, 10 patients with primary biliary cirrhosis (PBC), three patients with primary sclerosing cholangitis (PSC) and 20 chronic hepatitis patients with hepatitis C virus (HCV) infection were immunostained for IgG4. We investigated the relationship among the histopathology, the responses to steroid therapy and the IgG4 staining. Results: Nine of the 26 liver specimens from patients with AIH showed positive staining for IgG4 whereas none of the 10 samples from patients with PBC, the three samples from patients with PSC or the 20 samples from patients with HCV hepatitis were positive. Patients with IgG4‐positive AIH also showed increased serum levels of IgG. The numbers of T cells, B cells and plasma cells were significantly increased in the livers of patients with IgG4‐positive AIH as compared with those patients with IgG4‐negative AIH. Patients with IgG4‐positive AIH also showed a marked response to prednisolone therapy. Conclusions: AIH may be classified into either an IgG4‐associated type or an IgG4 non‐associated type with the former showing a marked response to prednisolone treatment.     

Diagnostic procedures for IgG4-related sclerosing cholangitis

Background/purpose

IgG4-related sclerosing cholangitis (IgG4-SC) is one of several diseases associated with autoimmune pancreatitis (AIP). However, diffuse cholangraphic abnormalities seen in association with AIP may resemble those seen in primary sclerosing cholangitis (PSC), and the presence of segmental stenosis suggests cholangiocarcinoma. IgG4-SC responds well to steroid therapy, whereas in contrast, liver transplantation is the only effective therapy for PSC, and surgical intervention is also needed for cholangiocarcinoma. The aim of this review was to establish the diagnostic procedures for IgG4-SC.

Methods

A literature search was conducted, covering English-language articles dealing with IgG4-SC published between 1991 and March 2010. As clinical data on IgG4-SC are limited, the author also took into consideration his own clinical experience with the treatment of IgG4-SC over a period of more than 19 years.

Results

When intrapancreatic stenosis is detected, pancreatic cancer should be ruled out. If multiple intrahepatic stenosis is evident, PSC should be discriminated on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining. An association with inflammatory bowel disease (IBD) is suggestive of PSC. If stenosis is demonstrated in the hepatic hilar region, cholangiocarcinoma should be discriminated by US, EUS, IDUS, and bile duct biopsy.

Conclusion

For diagnosis of IgG4-SC, coexistence of AIP is the most useful finding. However, the most important consideration for clinicians is to be aware of IgG4-SC when encountering patients with obstructive jaundice.     

Sclerosing cholecystitis associated with autoimmune pancreatitis

AIM: To evaluate the histopathological and radiological findings of the gallbladder in patients with autoimmune pancreatitis (AIP). METHODS: The radiological findings of the gallbladder of 19 AIP patients were retrospectively reviewed. Resected gallbladders of 8 AIP patients were examined histologically and were immunostained with anti- IgG4 antibody. Controls consisted of gallbladders resected for symptomatic gallstones (n = 10) and those removed during pancreatoduodenectomy for pancreatic carcinoma (n = 10), as well as extrahepatic bile ducts and pancreases removed by pancreatoduodenectomy for pancreatic carcinoma (n = 10). RESULTS: Thickening of the gallbladder wall was detected by ultrasound and/or computed tomography in 10 patients with AIP (3 severe and 7 moderate); in these patients severe stenosis of the extrahepatic bile duct was also noted. Histologically, thickening of the gallbladder was detected in 6 of 8 (75%) patients with AIP; 4 cases had transmural lymphoplasmacytic infiltration with fibrosis, and 2 cases had mucosal-based lymphoplasmacytic infiltration. Considerable transmural thickening of the extrahepatic bile duct wall with dense fibrosis and diffuse lymphoplasmacytic infiltration was detected in 7 patients. Immunohistochemically, severe or moderate infiltration of IgG4-positive plasma cells was detected in the gallbladder, bile duct, and pancreas of all 8 patients, but was not detected in controls. CONCLUSION: Gallbladder wall thickening with fibrosis and abundant infiltration of IgG4-positive plasma cells is frequently detected in patients with AIR We propose the use of a new term, sclerosing cholecystitis, for these cases that are induced by the same mechanism as sclerosing pancreatitis or sclerosing cholangitis in AIR     

First case of IgG4-related sclerosing cholangitis associated with autoimmune hemolytic anemia

To our knowledge, patients with immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) associated with autoimmune hemolytic anemia (AIHA) have not been reported previously. Many patients with IgG4-SC have autoimmune pancreatitis (AIP) and respond to steroid treatment. However, isolated cases of IgG4-SC are difficult to diagnose. We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis. The patient was a 73-year-old man who was being treated for dementia. Liver dysfunction was diagnosed on blood tests at another hospital. Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis, but a rapidly progressing anemia developed simultaneously. After the diagnosis of AIHA, steroid treatment was begun, and the biliary stricture improved. IgG4-SC without AIP was thus diagnosed.     

Intraductal papillary mucinous neoplasm of the pancreas and IgG4-related disease: A coincidental association

Background/aimsCoexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates.MethodsSerum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant.ResultsSerum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN.ConclusionsIn a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.     

Serum free light chain assessment in type 1 autoimmune pancreatitis

Background/Object: Some patients with type 1 autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease, have normal serum IgG4. The aim of this study is to investigate the diagnostic value of measuring serum free light chains (FLCs) in type 1 AIP.Materials and methodsThirty-seven patients with type 1 AIP, and 21 healthy, 17 alcoholic chronic pancreatitis (ACP), 21 idiopathic chronic pancreatitis (ICP) and 20 pancreatic cancer (PC) patients were enrolled. Serum IgG4 and FLC concentrations were measured using sFLC Freelite assays on a nephelometric analyzer.ResultsActive AIP patients have significantly higher serum levels of κ (median 30.97 (12.3–227.0) mg/L) and λFLC (median 20.53 (12.36–102.7) mg/L)) than healthy controls (κFLC; median 12.5 (3.1–52.1) mg/L), λFLC: median 12.45 (5.4–39.5) mg/L) (p < 0.05) correlating with raised serum IgG4, and significantly higher summated FLCs (∑) (median 53.09 (25.0–218.0) mg/L) than ICP patients (median 26.77 (15.0–89.2) mg/L) and healthy controls (median 24.43 (8.5–91.6) mg/L) (p < 0.05). AIP patients (median 1.43 (0.84–3.24)) showed significantly higher κ/λ ratios than ACP (median 0.83 (0.42–1.18)), ICP (median 0.87 (0.47–2.16)), PC patients (median 0.90 (0.48–1.27)) and healthy controls (median 0.963 (0.51–1.32)). There was a correlation between increased κ and λ FLCs levels and the number of affected organs involved in IgG4 related disease.ConclusionPatients with type 1 AIP have increased serum k and λ FLC concentrations, Σ FLC, and κ/λ ratios. These novel biomarkers may be useful in the diagnosis of type 1 AIP and in monitoring disease activity.     

A new clinicopathological entity of IgG4-related autoimmune disease

Background Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases.Methods To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies.Results In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls.Conclusions These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved.     

IgG4-unrelated type 1 autoimmune pancreatitis

A 50-year-old male was referred to our hospital for the evaluation of hyperproteinemia.Fluorodeoxyglucose positron emission tomography revealed high fluorodeoxyglucose uptake in the pancreas,bilateral lacrimal glands,submandibular glands,parotid glands,bilateral pulmonary hilar lymph nodes,and kidneys.Laboratory data showed an elevation of hepatobiliary enzymes,renal dysfunction,and remarkably high immunoglobulin(Ig) G levels,without elevated serum IgG4.Abdominal computed tomography revealed swelling of the pancreatic head and bilateral kidneys.Endoscopic retrograde cholangiopancreatography showed an irregular narrowing of the main pancreatic duct in the pancreatic head and stricture of the lower common bile duct.Histological examination by endoscopic ultrasonography-guided fine-needle aspiration revealed findings of lymphoplasmacytic sclerosing pancreatitis without IgG4-positive plasma cells.Abnormal laboratory values and the swelling of several organs were improved by the treatment with steroids.The patient was diagnosed as having type 1 autoimmune pancreatitis(AIP) based on the International Consensus Diagnostic Criteria.Therefore,we encountered a case of compatible type 1 AIP without elevated levels of serum IgG4 or IgG4-positive plasma cells.This case suggests that AIP phenotypes are not always associated with IgG4.     

Recent Advances in the Concept and Pathogenesis of IgG4-Related Disease in the Hepato-Bilio-Pancreatic System

Recent studies have proposed nomenclatures of type 1 autoimmune pancreatitis (AIP) (IgG4-related pancreatitis), IgG4-related sclerosing cholangitis (IgG4-SC), IgG4-related cholecystitis, and IgG4-related hepatopathy as IgG4-related disease (IgG4-RD) in the hepato-bilio-pancreatic system. In IgG4-related hepatopathy, a novel concept of IgG4-related autoimmune hepatitis (AIH) with the same histopathological features as AIH has been proposed. Among organs involved in IgG4-RD, associations with pancreatic and biliary lesions are most frequently observed, supporting the novel concept of “biliary diseases with pancreatic counterparts.” Targets of type 1 AIP and IgG4-SC may be periductal glands around the bile and pancreatic ducts. Based on genetic backgrounds, innate and acquired immunity, Th2-dominant immune status, regulatory T (Treg) or B cells, and complement activation via a classical pathway may be involved in the development of IgG4-RD. Although the role of IgG4 remains unclear in IgG4-RD, IgG4-production is upregulated by interleukin 10 from Treg cells and by B cell activating factor from monocytes/basophils with stimulation of toll-like receptors/nucleotide-binding oligomerization domain-like receptors. Based on these findings, we have proposed a hypothesis for the development of IgG4-RD in the hepato-bilio-pancreatic system. Further studies are necessary to clarify the pathogenic mechanism of IgG4-RD.     

Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease

Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. Many new clinical aspects of AIP have been clarified during the past 10 years, and AIP has become a distinct entity recognized worldwide. However, its precise pathogenesis or pathophysiology remains unclear. As AIP dramatically responds to steroid therapy, accurate diagnosis of AIP is necessary to avoid unnecessary surgery. Characteristic dense lymphoplasmacytic infiltration and fibrosis in the pancreas may prove to be the gold standard for diagnosis of AIP. However, since it is difficult to obtain sufficient pancreatic tissue, AIP should be diagnosed currently based on the characteristic radiological findings (irregular narrowing of the main pancreatic duct and enlargement of the pancreas) in combination with serological findings (elevation of serum γ-globulin, IgG, or IgG4, along with the presence of autoantibodies), clinical findings (elderly male preponderance, fluctuating obstructive jaundice without pain, occasional extrapancreatic lesions, and favorable response to steroid therapy), and histopathological findings (dense infiltration of IgG4-positive plasma cells and T lymphocytes with fibrosis and obliterative phlebitis in various organs). It is apparent that elevation of serum IgG4 levels and infiltration of abundant IgG4-positive plasma cells into various organs are rather specific to AIP patients. We propose a new clinicopathological entity, “IgG4-related sclerosing disease”, and suggest that AIP is a pancreatic lesion reflecting this systemic disease.     

Clinical and pathological differences between serum immunoglobulin G4-positive and -negative type 1 autoimmune pancreatitis

AIM: To identify clinical and pathological differences between serum immunoglobulin G4 (IgG4)-positive (SIP) and IgG4-negative (SIN) type 1 autoimmune pancreatitis (AIP) in South Korea. METHODS: AIP was diagnosed by the international consensus diagnostic criteria. The medical records and pathology were retrospectively reviewed and IgG4-positive cells were counted in a high power field (HPF). Type I AIP was defined as a high serum level of IgG4or histological finding. SIN type 1 AIP was defined as a histological evidence of type 1 AIP and a normal serum IgG4 level. The clinical and pathological findings were compared between the two groups. The analysis was performed using Student’s t test, Fischer’s exact test and Mann-Whitney’s U test. A P value of < 0.05 was considered statistically significant. As repeated com- parison was made, P values of less than 5% (P < 0.05) were considered significant. RESULTS: Twenty five patients with definite type 1 AIP (19 histologically and six serologically diagnosed cases) were enrolled. The mean tissue IgG4 concentrations were significantly higher in SIP than SIN group (40 cells per HPF vs 18 cells per HPF, P = 0.02). Among eight SIN patients, the tissue IgG4 concentrations were less than 15 cells per HPF in most of cases, except one. The sensitivity of serum IgG4 was 68% (17 SIP and eight SIN AIP). Other organ involvement was more frequent- ly associated with SIP than SIN AIP (59% vs 26%, P = 0.016). However, the relapse rate and diffuse swelling of the pancreas were not associated with serum IgG4 level. The concentrations of IgG4-positive cells per HPF were higher in SIP than SIN AIP (40 vs 18, P = 0.02). CONCLUSION: The sensitivity of serum IgG4 was 68% in type 1 AIP. High serum IgG4 level was associated with other organ involvement and tissue IgG4 concentration but did not affect the relapse rate in type 1 AIP.     

Association between autoimmune pancreatitis and systemic autoimmune diseases

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4).METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT).RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sjögren’s syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto’s thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level.CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.     

Schistosoma haematobium infection levels determine the effect of praziquantel treatment on anti-schistosome and anti-mite antibodies

Field studies show an association between schistosome infection and atopy, but the effects of anti-helminthic treatment on this association have not yet been investigated in human populations with different schistosome endemicity levels. This study aimed to compare the effects of anti-helminthic treatment on responses directed against the house dust mite Dermatophagoides pteronyssinus (Derp1) and Schistosoma haematobium in Zimbabwean populations living in high and low schistosome infection areas. Derp1- and schistosome-specific IgE and IgG4 antibodies were quantified by ELISA before and 6 weeks after anti-helminthic treatment. Following treatment, there were changes in the immune responses, which varied with place of residence. After allowing for the effects of sex, age and baseline infection intensity, there was no significant treatment effect on the change in anti-schistosome IgE and IgG4 in the high infection area. However, the anti-schistosome IgE/IgG4 ratio increased significantly, while anti-Derp1 IgE responses decreased as a result of treatment. In the low infection area, treatment resulted in a significant increase in anti-worm IgE levels, but there was no significant treatment effect on anti-schistosome or anti-Derp1 IgE/IgG4 ratios. Thus, the study shows that the level of schistosome endemicity affects the host responses to schistosome and mite antigens following anti-helminthic treatment.     

Increase diagnostic accuracy in differentiating focal type autoimmune pancreatitis from pancreatic cancer with combined serum IgG4 and CA19-9 levels

Background/objectivesTo distinguish autoimmune pancreatitis (AIP), especially focal type, from pancreatic cancer, is a greatest challenge for clinician. The aim of the study is to compare the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of combined serum IgG4 and CA19-9 levels to differentiate AIP from pancreatic cancer by HISORt, Asian and international consensus diagnostic criteria.MethodsWe measured serum IgG4, CEA, and CA19-9 levels in 188 AIP patients, 86 non-AIP chronic pancreatitis patients, and 130 pancreatic cancer patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were compared with different diagnostic criteria. We also compared the diagnostic performance in patients with or without jaundice.ResultsThe serum level of IgG4 was significantly higher in AIP than those in non-AIP chronic pancreatitis and pancreatic cancer. The optimal cutoffs of IgG4 and CA19-9 to differentiate AIP from pancreatic cancer were 175 mg/dL and 85.0 U/ml based on ROC analysis. Combining IgG4 level over 280 mg/dL and CA19-9 below 85.0 U/ml could yield a best diagnostic accuracy (85.6%) to distinguishing AIP from pancreatic cancer in all of the HISORt, Asian and international consensus diagnostic criteria. With the combination of serological test, focal type AIP could be diagnosed with comparable accuracy as diffuse type AIP.ConclusionsOur study demonstrated that combined use of serum IgG4 (over 280 mg/dL) and CA19-9 9 (below 85.0 U/ml) together increases the diagnostic accuracy to distinguish AIP from pancreatic cancer non-invasively, especially in focal type autoimmune pancreatitis.