P.03.10 IGG4-RELATED DISEASE RESPONDER INDEX BUT NOT SERUM IGG4 CORRELATES WITH DISEASE ACTIVITY AND THE RISK OF 1-YEAR RELAPSE IN TYPE 1 AUTOIMMUNE PANCREATITIS

Abstract IgG4-related disease (IgG4-RD) is a multi-organ autoimmune disease characterized by elevated serum IgG4 concentration. Although serum IgG4 concentration is widely used as a biomarker for IgG4-RD and type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of IgG4-RD, a significant number of patients have normal serum IgG4 levels, even in the active phase of the disease. Recently, we reported that the development of experimental AIP and human type 1 AIP is associated with increased expression of IFN-α and IL-33 in the pancreas. In this study, we assessed the utility of serum IFN-α and IL-33 levels as biomarkers for type 1 AIP and IgG4-RD. Serum IFN-α and IL-33 concentrations in patients who met the diagnostic criteria for definite type 1 AIP and/or IgG4-RD were significantly higher than in those with chronic pancreatitis or in healthy controls. Strong correlations between serum IFN-α, IL-33, and IgG4 concentrations were observed. Diagnostic performance of serum IFN-α and IL-33 concentrations as markers of type 1 AIP and/or IgG4-RD was comparable to that of serum IgG4 concentration, as calculated by the receiver operating characteristic curve analysis. Induction of remission by prednisolone treatment markedly decreased the serum concentration of these cytokines. We conclude that serum IFN-α and IL-33 concentrations can be useful as biomarkers for type 1 AIP and IgG4-RD.

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IgG4-Seronegative Autoimmune Pancreatitis and Sclerosing Cholangitis

Case Reports in Gastrointestinal Medicine ◽

10.1155/2015/591360 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6

Author(s):

Allon Kahn ◽

Anitha D. Yadav ◽

M. Edwyn Harrison

Keyword(s):

Autoimmune Pancreatitis ◽

Sclerosing Cholangitis ◽

Clinical Presentation ◽

Surgical Intervention ◽

Comprehensive Evaluation ◽

Elevated Serum ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Type 1 Autoimmune Pancreatitis

IgG4-related disease is a relatively novel clinical entity whose gastrointestinal manifestations include type 1 autoimmune pancreatitis (AIP) and IgG4-associated sclerosing cholangitis. The presence of elevated serum IgG4 is suggestive but not essential for the diagnosis of type 1 AIP and is a pervasive feature of the proposed diagnostic criteria. The differential diagnosis of type 1 AIP includes malignant conditions, emphasizing the importance of a deliberate, comprehensive evaluation. Management of patients with a suggestive clinical presentation, but without serum IgG4 elevation, is difficult. Here we present three cases of IgG4-seronegative AIP and sclerosing cholangitis that responded to empiric steroid therapy and discuss approach considerations. These cases demonstrate the value of meticulous application of existing diagnostic algorithms to achieve a clinical diagnosis and avoid surgical intervention.

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A Case of Type 1 Autoimmune Pancreatitis (AIP), a Form of IgG4-Related Disease (IgG4-RD)

American Journal of Case Reports ◽

10.12659/ajcr.904263 ◽

2017 ◽

Vol 18 ◽

pp. 822-825 ◽

Cited By ~ 3

Author(s):

Mounira El Euch ◽

Souha Hddad ◽

Madiha Mahfoudhi ◽

Hela Maktouf ◽

Fethi Ben Hamida ◽

...

Keyword(s):

Autoimmune Pancreatitis ◽

Related Disease ◽

Igg4 Related Disease ◽

Type 1 Autoimmune Pancreatitis

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A Follow-Up Study of a European IgG4-Related Disease Cohort Treated with Rituximab

Journal of Clinical Medicine ◽

10.3390/jcm10061329 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1329

Author(s):

Johanna Backhus ◽

Christian Neumann ◽

Lukas Perkhofer ◽

Lucas A Schulte ◽

Benjamin Mayer ◽

...

Keyword(s):

Disease Activity ◽

Clinical Activity ◽

Inflammatory Disorder ◽

International Consensus ◽

Steroid Pulse ◽

Related Disease ◽

Igg4 Related Disease

Objectives: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although long-term data are lacking. We aimed to bridge this gap with a cohort of IgG4-RD patients treated with RTX and to assess the potential value of the Responder Index (RI) as a discriminatory score for disease activity. Methods: We retrospectively evaluated 46 patients from a tertiary referral centre who were diagnosed with IgG4-RD and/or type 1 AIP according to the International Consensus Diagnostic Criteria or Unifying-AIP criteria between June 2006 and August 2019. Results: Patients resembled previous cohorts in terms of characteristics, diagnosis, and therapeutic response. Thirteen of the 46 patients with IgG4-RD/type 1 AIP were treated with RTX pulse therapy due to relapse, adverse reactions to steroids, or high-risk constellations predicting a severe course of disease with multi-organ involvement. Median follow-up after diagnosis was 52 months for all subjects, and 71 months in IgG4-RD patients treated with RTX. While patients in the RTX group showed no significant response to an initial steroid pulse, clinical activity as measured by the RI significantly decreased in the short-term after RTX induction. Within 16 months, 61% of patients relapsed in the RTX group but responded well to re-induction. Clinical and laboratory parameters improved equally in response to RTX. Conclusion: RTX therapy in patients with IgG4-RD is an effective and safe treatment to induce treatment response and possible long-term remission. Repeated RTX administration after 6–9 months may be of value in reducing the risk of relapse. The RI appears to be a reasonable index to assess disease activity and to identify patients with IgG4-related disease who may benefit from B-cell-depleting therapy.

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Soluble Interleukin-2 Receptor: A Potential Marker for Monitoring Disease Activity in IgG4-Related Disease

Mediators of Inflammation ◽

10.1155/2018/6103064 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 12

Author(s):

A. F. Karim ◽

L. E. M. Eurelings ◽

R. D. Bansie ◽

P. M. van Hagen ◽

J. A. M. van Laar ◽

...

Keyword(s):

Disease Activity ◽

Interleukin 2 ◽

Elevated Serum ◽

Related Disease ◽

Interleukin 2 Receptor ◽

Igg4 Related Disease ◽

Potential Marker ◽

Potential Biomarker ◽

Serum Igg4 ◽

Soluble Interleukin 2 Receptor

Background. IgG4-related disease (IgG4-RD) is a fibroinflammatory condition. T-cells play a crucial role in the pathogenesis, and therefore, serum soluble interleukin-2 receptor (sIL-2R) may be a potential biomarker. Method. We studied the levels of sIL-2R in 26 histologically proven IgG4-RD patients with available serum sIL-2R and compared them to those in newly diagnosed and untreated sarcoidosis patients (n=78) and controls (n=101) and the serum sIL-2R levels in patients after treatment of IgG4-RD (n=15). The disease activity was measured using the IgG4-Related Disease Responder Index (IgG4-RD RI). Results. Median serum sIL-2R in IgG4-RD patients was 4667 pg/ml compared to 1515 pg/ml in controls (P<0.001) and 6050 pg/ml in sarcoidosis patients (P=0.004 compared to IgG4-RD). All IgG4-RD patients had elevated serum sIL-2R levels compared to the reference value of <2500 pg/ml in controls and 85% elevated serum IgG4; however, these did not correlate with each other. Both serum sIL-2R and IgG4 levels declined significantly after treatment (P=0.001 and P=0.01, resp.). Before treatment, serum sIL-2R level and IgG4-RD RI did not correlate with each other. However, the decrease in serum sIL-2R upon treatment did correlate significantly (P=0.04) with the decrease in disease activity assessed by IgG-RD RI. Conclusion. Serum sIL-2R is elevated in IgG4-RD reflecting the inflammatory process with enhanced T-cell activation. Furthermore, serum sIL-2R might serve as a potential marker of response to treatment in IgG4-RD.

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Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis

International Journal of Surgical Pathology ◽

10.1177/1066896920924781 ◽

2020 ◽

Vol 28 (8) ◽

pp. 844-849

Author(s):

Rie Nakata ◽

Takeshi Uehara ◽

Mai Iwaya ◽

Shiho Asaka ◽

Shota Kobayashi ◽

...

Keyword(s):

Autoimmune Pancreatitis ◽

Plasma Cells ◽

Tumor Formation ◽

Mean Values ◽

Serum Igg4 ◽

Type 1 Autoimmune Pancreatitis ◽

Immunoglobulin G Subclass ◽

Antibody Cocktail ◽

Focal Tumor

Background. Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4 + plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG+ cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD. Methods. We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists. Results. Although mean values for IgG+ cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; P = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; y[IgG] = 0.988 x + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent. Conclusion. AC-IgG could replace IgG to count IgG+ cells because of its lower Cv.

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The Utility of Serum IgG4 Concentrations as a Biomarker

International Journal of Rheumatology ◽

10.1155/2012/198314 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 24

Author(s):

Shigeyuki Kawa ◽

Tetsuya Ito ◽

Takayuki Watanabe ◽

Masahiro Maruyama ◽

Hideaki Hamano ◽

...

Keyword(s):

Autoimmune Pancreatitis ◽

Plasma Cells ◽

High Serum ◽

Wall Thickening ◽

Systemic Involvement ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Long Term Follow Up ◽

Characteristic Features

IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1) systemic involvement; (2) solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3) high serum IgG4 concentration >135 mg/dL; (4) abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5) a positive response to corticosteroid therapy; and (6) complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease.

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IgG4-related aortitis/periaortitis and periarteritis: a distinct spectrum of IgG4-related disease

10.21203/rs.3.rs-16955/v1 ◽

2020 ◽

Author(s):

Linyi Peng ◽

Panpan Zhang ◽

Jieqiong Li ◽

Zheng Liu ◽

Hui Lu ◽

...

Keyword(s):

Thoracic Aorta ◽

Abdominal Aorta ◽

Iliac Artery ◽

Treatment Efficacy ◽

Male Predominance ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Type 3

Abstract Background: Large vessels could be involved in IgG4-related disease(IgG4-RD).This study aimed to clarify the clinical features and evaluate the treatment efficacy for IgG4-RD with aortitis/periaortitis and periarteritis (PAO/PA). Methods: This study enrolled 587 IgG4-RD patients in a prospective cohort with a follow-up time for more than 6 months. The distribution of IgG4-related PAO/PA was classified into four types: type 1, thoracic aorta; type 2a, abdominal aorta; type 2b, abdominal aorta and iliac artery; type 2c, iliac artery; type 3, thoracic and abdominal aorta; type 4, other arteries. Patient’s demographic data, clinical characteristics, laboratory parameters, and treatment efficacy were analyzed. Results: Of 587 IgG4-RD patients, 89(15.2%) had PAO/PA. The average age was 58.3±11.1 years, with male predominance (85.4%). Vessels affected were as follows: abdominal aorta (83.1%), iliac artery (70.8%), thoracic aorta (13.5%) and other vessels (13.5%). The most prevalent distribution type of IgG4-related PAO/PA was type 2b, with 74 (83.1%) patients, followed by type 2a, type 2c, type 3, and type 1. 55 (61.8%) PAO/PA patients had hydronephrosis, with renal insufficiency occurred in 43 (48.3%), and 31 (34.8%) PAO/PA patients had D-J stent drainage due to severe ureteral obstruction. After treatment with glucocorticoid and immunosuppressants, 82% patients achieved a remission with shrinking of perivascular mass. Conclusions: IgG4-RD with PAO/PA was distinct from non-PAO/PA in demographic features, organs involvement distribution, inflammatory markers, serum IgG4 and IgE. The most common affected vessel was abdominal aorta, and most patients responded well with treatment.

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Intraductal Tubulopapillary Epithelial Proliferation Associated with Type 1 Autoimmune Pancreatitis

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.271.fuj ◽

2018 ◽

Vol 27 (1) ◽

pp. 83-87 ◽

Cited By ~ 2

Author(s):

Shinya Fujie ◽

Hiroyuki Matsubayashi ◽

Hirotoshi Ishiwatari ◽

Hiromasa Hazama ◽

Takaaki Ito ◽

...

Keyword(s):

Pancreatic Duct ◽

Autoimmune Pancreatitis ◽

Fibrous Tissue ◽

Ductal Adenocarcinoma ◽

Epithelial Proliferation ◽

Pancreatic Body ◽

Gastric Type ◽

Serum Igg4 ◽

Type 1 Autoimmune Pancreatitis

A 70-year-old man was referred to our hospital with exacerbation of diabetes. His blood tests showed elevated levels of serum IgG4 and HbA1c. Computed tomography of the pancreatic body demonstrated a weakly enhanced mass, 2 cm in size, with indistinct borders. Magnetic resonance cholangiopancreatography revealed a narrowing of the main pancreatic duct (MPD) at the pancreatic body, a markedly dilated upstream duct, and a slightly dilated downstream duct. Endoscopic ultrasonography demonstrated an iso-hypoechoic heterogeneous mass, protruding and spreading in the pancreatic duct. The histology of a fine needle aspiration sample demonstrated fibrous tissue containing abundant IgG4-positive plasma cells and atypical epithelial cells. The imaging findings and histology were not typical for either pancreatic ductal adenocarcinoma or type 1 autoimmune pancreatitis (AIP), but these were not completely excluded, and a distal pancreatectomy was performed. Histological examination showed an intraductal tubulopapillary epithelial proliferation, which contained cytoplasmic mucin (MUC5AC and MUC6), and severe IgG4-positive lymphoplasmacytic infiltration in the interstitium around the MPD. Next-generation sequencing using DNA extracted from the tumor revealed no mutation of K-ras, GNAS, or TP53. The entire lesion was ultimately diagnosed as AIP with an intraductal tubular and papillary epithelial hyperplasia producing gastric-type mucin. Some recent reports have described AIP development in the background of intraductal papillary mucinous neoplasms, and some have hypothesized a paraneoplastic occurrence of IgG4-related disease. The current case indicates issues in the clinical diagnosis of rare variants of AIP, and raises questions about the relationship between AIP and pancreatic epithelial lesions.

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