IgG4-Related Diseases in the Gastrointestinal Tract: Clinical Presentation, Diagnosis and Treatment Challenges

Backhus, J; Seufferlein, Thomas; Perkhofer, Lukas; Hermann, Patrick C.; Kleger, Alexander

doi:10.1159/000492814

Cited by 13 publications

(12 citation statements)

References 46 publications

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“…While previous studies have proposed established diseasemodifying antirheumatic drugs (DMARDs) such as azathioprine, recent data suggest more precise interventions, such as the B-cell-depleting agent RTX, to interrupt the pathophysiological cascade of events in IgG4-RD [17,23]. While data on RTX treatment response are becoming more frequent, follow-up data on remission and relapse rates on RTX therapy remain sparse [22,24,25]. With our study, we bridge this gap in the knowledge and present a European IgG4-RD cohort of 46 patients initially treated with steroids who received treatment with RTX when meeting the criteria of (i) steroid-dependent IgG4-RD, (ii) relapse, or (iii) severe multi-organ involvement.…”

Section: Discussionmentioning

confidence: 99%

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

Backhus

Neumann

Perkhofer

et al. 2021

JCM

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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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Section: Discussionmentioning

confidence: 99%

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

Backhus

Neumann

Perkhofer

et al. 2021

JCM

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“…Autoimmune pancreatitis (AIP) type-1 belongs to the group of immunoglobulin G4 (IgG4)-related diseases. The characteristic signs of this disease group are chronic inflammatory reaction, pronounced fibrotization of tissues and presence of mononuclear inflammatory infiltrate with plasma cells positive for IgG4[ 48 ]. IgG4 is an immunoglobulin that is among the least represented across the immunoglobulin spectrum, making up less than 5% of that spectrum overall[ 49 ].…”

Section: H Pylori and Autoimmune Pancreatitismentioning

confidence: 99%

“…In 2018, Backhus et al [ 48 ] published a paper summarizing new pathways in the pathogenesis of IgG4-related diseases[ 48 ]. One mechanism may be the transformation from beta cells to plasma cells and activation of eosinophilic granulocytes associated with the secretion of proinflammatory cytokines.…”

Section: H Pylori and Autoimmune Pancreatitismentioning

confidence: 99%

Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis

Kunovský

Dítě

Jabandžiev

et al. 2021

WJGO

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Helicobacter pylori ( H. pylori ) is an infectious agent influencing as much as 50% of the world’s population. It is the causative agent for several diseases, most especially gastric and duodenal peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach. A number of other, extragastric manifestations also are associated with H. pylori infection. These include neurological disorders, such as Alzheimer’s disease, demyelinating multiple sclerosis and Parkinson’s disease. There is also evidence for a relationship between H. pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma. Generally little is known about the relationship between H. pylori infection and diseases of the pancreas. Most evidence about H. pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis. There is data (albeit not fully consistent) indicating modestly increased pancreatic cancer risk in H. pylori -positive patients. The pathogenetic mechanism of this increase is not yet fully elucidated, but several theories have been proposed. Reduction of antral D-cells in H. pylori -positive patients causes a suppression of somatostatin secretion that, in turn, stimulates increased secretin secretion. That stimulates pancreatic growth and thus increases the risk of carcinogenesis. Alternatively, H. pylori , as a part of microbiome dysbiosis and the so-called oncobiome, is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation. The role of H. pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins (mostly enzymes) of H. pylori and pancreatic tissue. Patients with autoimmune pancreatitis often show positivity for antibodies against H. pylori proteins. H. pylori , as a part of microbiome dysbiosis, also is viewed as a potential trigger of autoimmune inflammation of the pancreas. It is precisely these relationships (and associated equivocal conclusions) that constitute a center of attention among pancreatologists, immunologists and pathologists. In order to obtain clear and valid results, more studies on sufficiently large cohorts of patients are needed. The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research. Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer.

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“…Thus, reliable biomarkers are urgently warranted. 3 Previously, qPCR-based measurements of the IgG4/ IgG mRNA ratio that originate from dominant IgG4 + -B-cell receptor (BCR) clones have been proposed to fill this gap with "ideal" test characteristics (AUC 0.991, sensitivity 94%, specificity 98.7%). 4 In contrast, recent work from Beuers and colleagues found relevant limitations of IgG4/IgG qPCR ratio in distinguishing between IgG4-RD and pancreaticobiliary malignancies.…”

mentioning

confidence: 99%

IgG4-Related Diseases in the Gastrointestinal Tract: Clinical Presentation, Diagnosis and Treatment Challenges

Cited by 13 publications

References 46 publications

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

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

Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis

Serum IgG4 levels outperform IgG4/IgG RNA ratio in differential diagnosis of IgG4-related disease

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