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Flow chart illustrating the suggested pathophysiology of type 1 autoimmune pancreatitis (AIP). Decreased numbers of circulating naı¨venaı¨ve regulatory T cells and CD19 ? CD24 high CD27 ? regulatory B cells (Bregs) may participate in the initiation of type 1 AIP. Interleukin (IL)-35 stimulates the development of eTregs and progression of the disease, and an enhanced Th2 immune response. The production of immunoglobulin (Ig) G4 may be regulated through
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In 1995, Yoshida et al. proposed first the concept of “autoimmune pancreatitis” (AIP). Since then, AIP has been accepted as a new pancreatic inflammatory disease and is now divided two subtypes. Type 1 AIP affected immunoglobulin G4 (IgG4) and implicates the pancreatic manifestation of IgG4-related disease, while type 2 is characterized by neutroph...
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Context 1
... innate immunity, basophils cause inflammatory monocytes to differentiate into M2 macrophages, affecting the production of IgG4 via TLR signaling and influencing the Th2 immune environment. Also, M2 macrophages contribute to the development of fibrosis and stimulation of the Th2 immune reaction. Neutrophils also influence IgG4 production via NETs (Fig. ...
Citations
... On the other hand, circulating nTreg levels are low, a pattern consistent with immunosenescence. These abundant iTregs appear to be ineffective at controlling the inflammation, and a likely explanation for this is a decreased expression of Mammalian Sterile 20-like Kinase 1 (MST1), which is essential for allowing the cell-to-cell contact needed for iTregs to act on Teff cells [205]. Patients with IgG4-RD are at increased risk to both pancreatic cancer and lymphoma [206]. ...
When an antigen stimulates the immune system, specific T regulatory (Treg) and T effector (Teff) subpopulations develop from naïve T cells. The Treg cell population will produce the memory Treg (mTreg) cells against that specific antigen. An inappropriate homeostatic balance among Teff, Treg and mTreg cells can direct the immune system toward either cancer or autoimmunity. When cancer is present, Treg cells suppress anti-tumor immunity, and, when cancer is absent, Treg cells play the beneficial role of preventing the development of autoimmunity. In this review, we analyze Treg responses after SARS-CoV-2 mRNA vaccination and find distinct pathological responses under differing conditions. In cancer patients, the degree of disease progression depends on the cancer status at the time of vaccination and the type of cancer treatment they receive concurrently. We hypothesize that migration of circulating dendritic cells and mTreg cells back to the thymus accelerates thymic involution, a direct cause of immunosenescence. In summary, the Treg responses produced after mRNA vaccination and the subsequent mRNA-encoded SARS-CoV-2 spike protein expression may lead to a harmful influence on the immune system of vaccinees, and subsequent accelerated development of cancer and autoimmune disease. These mechanisms are consistent with both epidemiological findings and case reports.
... Pancreatic parenchymal and ductal imaging, serology, pancreatic histology, involvement of other organs, and response to steroid therapy are among the diagnostic criteria for AIP [7]. Serum IgG4 concentration, though not ideal, is a commonly used biomarker, and other serological markers, such as hypocomplementemia, antinuclear antibodies, rheumatoid factor positivity, and specific autoantibodies, have been investigated. ...
... Serum IgG4 concentration, though not ideal, is a commonly used biomarker, and other serological markers, such as hypocomplementemia, antinuclear antibodies, rheumatoid factor positivity, and specific autoantibodies, have been investigated. The cutoff value for serum IgG4 is confirmed at 140 mg/dL [7]. Histopathological evaluation involves assessing IgG4 immunostaining of the duodenal papilla, neutrophil infiltration and molecular markers like IFN-α and IL-33, which are considered valuable for diagnosis and monitoring. ...
... Radiological imaging reveals diffuse pancreatic swelling, irregular narrowing of the main pancreatic duct, and characteristic patterns on dynamic computed tomography and contrast-enhanced magnetic resonance imaging. Endoscopic retrograde cholangiopancreatography typically shows narrowing of the main pancreatic duct, and magnetic resonance cholangiopancreatography may display multiple intermittent absences [7]. Endoscopic ultrasound (EUS) fineneedle aspiration is a useful technique for tissue sampling, especially in cases of focal AIP or when serum IgG4 levels are within normal limits [7]. ...
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 interleukin-33. AIP poses an increased risk of various malignancies, and the association 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.
... I gG4-асоційована хвороба (IgG4-АХ) -захворювання з невідомою етіологією і мультиорганним ураженням специфічним запальним процесом, що характеризується перидуктальною запальною інфільтрацією переважно СD4 + -Т-лімфоцитами, IgG4 + -плазмоцитами, сторіоформним фіброзом («муаровим», «вихро подібним», що формує специфічний малюнок, схожий на «циновку», з різнонаправленим розташуванням фіброзних пучків), атрофією ацинарної тканини, яка часто призводить до стенозу протоки підшлункової залози (ПЗ) [3,31,33]. Відбувається поєднане синхронне чи метахронне залучення в патологічний процес великої кількості органів-мішеней, лише у 10 -20 % пацієнтів спостерігається лише одна первинна локалізація патологічного процесу без ураження інших органів. Хворіють переважно чоловіки середнього та похилого віку. ...
... Хворі серонегативні з відсутністю залучення до запального процесу інших органів. Для встановлення остаточного діагнозу необхідно провести морфологічне дообстеження пацієнтів [31,32]. ...
... Під час ультразвукового дослідження (УЗД) черевної порожнини виявляють дифузне чи локальне гіпоехогенне ураження ПЗ, дифузне звуження і нерівності головної панкреатичної протоки. Через подібність симптомів з такими інших форм панкреатиту діагноз АІП не завжди встановлюють [1,31]. ...
IgG4‑associated disease is a disorder with an unknown etiology and multi‑organ damage caused by a specific inflammatory process, characterized by periductal inflammatory infiltrate mainly by CD4+‑T lymphocytes, IgG4+‑plasma cells, storiform fibrosis, atrophy of acinar tissue, which often results in pancreatic duct stenosis. A great number of target organs are involved in the pathological process, one primary localization of the pathological process without damage to other organs is observed in only 10 — 20% of patients. Mostly affected are middle‑aged and elderly men. The pathological process is stipulated by a pronounced tissue infiltration with lymphocytes and plasma cells, followed by fibrosis development. The clinical picture varies widely, depending on the combination of affected target organs. The long‑term prognosis of the disease has not been sufficiently studied due to the small number of observations, the variety of clinical forms and the variability of treatment approaches. IgG4‑associated lesions have been described for localization in pancreas, biliary tract and gallbladder, liver, esophagus, stomach and intestines, retroperitoneal space, mammary glands and thyroid and prostate glands, salivary and lacrimal glands, kidneys and ureters, lymph nodes, skin and bones. The article presents a review of current literature on gastroenterological lesions in IgG4 associated diseases, as well as a clinical case of a patient with IgG4‑autoimmune pancreatitis type 1, IgG4‑sclerosing cholangitis, autoimmune hepatitis type 1 complicated by 3 type diabetes mellitus. The diagnosis of an IgG4‑associated disease in gastroenterological practice causes some difficulties. However, the timely diagnosis and administration of adequate treatment can significantly improve the quality of life of the patient and prevent the development of complications.
... Autoimmune pancreatitis (AIP) is a distinct form of pancreatic inflammatory disease that responds well to glucocorticoid therapy (1). AIP can be classified into types 1 and 2 based on clinical and pathological findings. ...
Background/Objectives
Autoimmune pancreatitis (AIP) is a distinct form of pancreatic inflammatory disease that responds well to glucocorticoid therapy. Knowledge on AIP has rapidly evolved over the past two decades. Based on bibliometric analysis, this study aimed to assess the research status of AIP over the past two decades and determine the research focus and emerging topics.
Methods
AIP-related publications published between January 1, 2002, and June 6, 2022, were retrieved from the Web of Science Core Collection. Bibliometric data were analyzed using HisCite, VOSviewer, CiteSpace, and bibliometrix package. Annual output, leading countries/regions, active institutions and authors, core journals and references, and keywords of AIP were evaluated.
Results
Overall, 1,772 publications were retrieved from 501 journals by 6,767 authors from 63 countries/regions. Japan published articles on AIP the most (n=728, 41.1%), followed by the United States (n=336, 19%), Germany (n=147, 8.3%), China (n=127, 7%), and Italy (n=107, 6%). The top three most prolific authors were Terumi Kamisawa from Tokyo Metropolitan Komagome Hospital (n=117), Kazuichi Okazaki from Kansai Medical University (n=103), and Shigeyuki Kawa from Matsumoto Dental University (n=94). Pancreas was the most productive journal regarding AIP research (n=95), followed by the Journal of Gastroenterology (n=67), Internal Medicine (n=66), Pancreatology (n=63), and World Journal of Gastroenterology (n=62). “Diagnosis” was the most mentioned keyword. “Risk,” “malignancy,” “outcome,” “22-gauge needle,” and “fine-needle aspiration” were recognized as emerging topics.
Conclusion
Japan was the leading country in AIP research. Research papers were mainly published in specialized journals. Diagnosis was the research focus. Long-term outcomes and pancreatic tissue acquisition were recognized as research frontiers for AIP.
Pancreas pathology is constantly evolving and can present various challenges for pathologists. This paper is focused on providing helpful hints for daily routine diagnostics. During histopathological analysis of pancreas biopsies, pancreatic ductal adenocarcinoma must be distinguished not only from other solid neoplasms, but especially from its mimicker, autoimmune pancreatitis. This can be achieved by a systematic workup following clear diagnostic criteria. When analyzing samples from cystic pancreatic lesions, mucin-producing neoplasms must be detected due to their role as pancreatic cancer precursors; molecular analyses can help considerably with their detection and distinction. During frozen section examination, evaluation of the pancreatic neck margin and analysis of unclear lesions of the liver are two important tasks, which are explained further in this article. A special challenge is the evaluation of neoadjuvant treated pancreatic cancer, which requires a detailed macroscopic and microscopic workup. Finally, current advances in precision oncology and emerging approaches for pancreatic cancer within this field are discussed. With the advancement of technical possibilities and their increasingly broad implementation, the classification systems in pancreatic pathology will continue to gain in complexity, but also in accuracy.
Background
The risk and prognosis of pancreatobiliary cancer and in patients with autoimmune pancreatitis (AIP) and IgG4‐related sclerosing cholangitis (IgG4‐SC) remain unclear. Therefore, we retrospectively investigated the risk of pancreatobiliary cancer and prognosis in patients with AIP and IgG4‐SC.
Methods
Patients with AIP and IgG4‐SC at seven centers between 1998 and 2022 were investigated. The following data were evaluated: (1) the number of cancers diagnosed and standardized incidence ratio (SIR) for pancreatobiliary and other cancers during the observational period and (2) prognosis after diagnosis of AIP and IgG4‐SC using standardized mortality ratio (SMR).
Results
This study included 201 patients with AIP and IgG4‐SC. The mean follow‐up period was 5.7 years. Seven cases of pancreatic cancer were diagnosed, and the SIR was 8.11 (95% confidence interval [CI]: 7.29–9.13). Three cases of bile duct cancer were diagnosed, and the SIR was 6.89 (95% CI: 6.20–7.75). The SMR after the diagnosis of AIP and IgG4‐SC in cases that developed pancreatobiliary cancer were 4.03 (95% CI: 2.83–6.99).
Conclusions
Patients with autoimmune pancreatitis and IgG4‐SC were associated with a high risk of pancreatic and bile duct cancer. Patients with AIP and IgG4‐SC have a worse prognosis when they develop pancreatobiliary cancer.
Este estudo teve como principal enfoque a evidenciação e discussão das manifestações clínicas presentes na pancreatite autoimune, sobretudo o tipo 1. Para isso, foi efetuada uma busca na base de dados PubMed, em que se utilizou os seguintes Descritores em Ciências da Saúde: autoimmune; pancreatitis; and; clinical; manifestations. Para um melhor delineamento foram selecionados apenas artigos publicados nos anos de 2022 a 2023, totalizando 13 artigos, dos quais foram excluídos 7, restando 6 para a análise e produção deste trabalho. A pancreatite autoimune é uma doença que ainda não possui epidemiologia global bem conhecida, no entanto, em pesquisa japonesa mais recente observou-se aumento nos casos da doença em comparação a pesquisa anterior, além disso esta doença além de ocasionar sintomas pancreáticos como dor abdominal e icterícia, pode acometer tecidos extrapancreáticos como o sistema biliar e o retroperitôneo. Desta forma, baseado nas complicações e nos dados epidemiológicos existentes, se faz necessário uma discussão acerca desta temática, com a finalidade de aumentar cada vez mais o nível de informações e evidências científicas em relação a este tema.
Background/Objectives
Proper assessment of disease activity and prediction of relapse are crucial for the management of autoimmune pancreatitis (AIP). The M-ANNHEIM-AiP-Activity-Score (MAAS) has been proposed to determine disease activity and predict relapse in German and Swedish patients with AIP. MAAS is calculated using six categories: pain report, pain control, exocrine insufficiency, endocrine insufficiency, imaging, and complications. This study aimed to clarify the usefulness of MAAS to predict relapse in Japanese patients with type 1 AIP.
Methods
We retrospectively analyzed 117 patients with type 1 AIP undergoing initial and maintenance steroid treatments at our institute between April 2006 and March 2021. AIP was diagnosed according to the Japanese Diagnostic Criteria for AIP 2018. We examined the association of MAAS with relapse during and after maintenance treatment.
Results
MAAS (median, 8 points) at the start of the initial treatment was reduced after treatment (median, 4 points; P < 0.001). A MAAS ≥11 points at the start of the initial treatment was associated with relapse. The initial treatment-induced reduction of MAAS ≥60% was lower in patients with relapse (median 47.7%) than in patients without relapse (median, 66.7%; P = 0.007). MAAS at the start of maintenance treatment was higher for patients with relapse (median, 6 points) than that for patients without relapse (median, 4 points; P = 0.007). MAAS ≥4 points at the start of maintenance treatment was associated with subsequent relapse.
Conclusions
MAAS is useful for predicting relapse in patients with type 1 AIP undergoing maintenance therapy.
