Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (792 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A spectrum of systemic autoimmune diseases in which immunoglobulin G4 plays a pathophysiologic role. It can affect multiple organs in highly variable presentations, characterized by inflammatory lesions composed of IgG4-positive plasma cells, further infiltrated by T helper cells (t-lymphocytes, helper-inducer) when linked to progressive fibrosis and eventual organ damage.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Immunoglobulin G4 Related Disease; Immunoglobulin G4-Related Diseases; IgG4-Associated Autoimmune Disease; Autoimmune Disease, IgG4-Associated; IgG4 Associated Autoimmune Disease; IgG4-Associated Autoimmune Diseases; IgG4-Related Disease; IgG4 Related Disease.
Where it fits in the MeSH classification
- Broader topics
- Autoimmune Diseases
Related concepts
- Immunoglobulin
- Plasma Cells
- T-Lymphocytes
- Helper-Inducer
- Fibrosis
Research landscape
PubMed indexes 1,939 records tagged with the MeSH heading “Immunoglobulin G4-Related Disease” (counts retrieved 2026-10-29). 1,587 of them (81.8%) were published from 2020 onward, and the busiest period so far is 2020 onward with 1,587 records.
Reviews account for 421 records (21.7%) and meta-analyses for 8. Randomized controlled trials number 8 (0.4%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 0 |
| 2010-2019 | 405 |
| 2020 onward | 1,587 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 421 | 21.7% |
| Meta-analyses | 8 | 0.4% |
| Randomized controlled trials | 8 | 0.4% |
Method: PubMed query "Immunoglobulin G4-Related Disease"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in immunology
Immune responses are studied in model organisms, in cells from donors and in patients, and the same pathway can behave differently across these settings. Mouse immune systems differ from human ones in important ways, and blood measurements may not reflect what happens in tissues. Clinical conclusions about immune-mediated disease or immunotherapy come mainly from controlled trials and long-term cohorts. Check the species and tissue studied, whether markers were linked to outcomes patients notice, and the follow-up time.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Thoracic manifestations of IgG4-related disease | 2023 | Review article Design not recorded in structured metadata | 41 | cc by PMID 36437514 · DOI · PMC10100266 |
| Current status of type 1 (IgG4-related) autoimmune pancreatitis | 2022 | Review article Design not recorded in structured metadata | 37 | cc by PMID 35916965 · DOI · PMC9522839 |
| IgG4 autoantibodies and autoantigens in the context of IgG4-autoimmune disease and IgG4-related disease | 2024 | Review article Design not recorded in structured metadata | 24 | cc by PMID 38433835 · DOI · PMC10904653 |
| Immunological Biomarkers to Assess Activity and Treatment Response in IgG4-Related Disease | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 41752722 · DOI · PMC12942627 |
Thoracic manifestations of IgG4-related disease [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Immunoglobulin G4-related disease (IgG4-RD) is a recently described rare systemic fibroinflammatory disease with an estimated incidence of less than 1 in 100,000 persons per year.
- Closing excerpt
- In this review, we summarize current knowledge regarding the pathophysiology, epidemiology, diagnostic modalities (clinical-biological-imaging-histopathology) and treatment of IgG4-RD thoracic involvement.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (239 words)
Immunoglobulin G4-related disease (IgG4-RD) is a recently described rare systemic fibroinflammatory disease with an estimated incidence of less than 1 in 100,000 persons per year. The disease can affect virtually any organ and is characterized by unifying histopathological findings. Recently, four subgroups of patients have been characterized: hepatobiliary, head and neck, Mikulicz syndrome and retroperitoneal fibrosis, who illustrate the mainly abdominal and ENT tropism of the disease. Yet, thoracic involvement is not uncommon. It can be detected in up to 30% of patients with systemic IgG4-RD and is the exclusive manifestation of the disease in about 10% of cases. Clinical symptoms are nonspecific and may include dyspnoea, cough or chest pain. Chest CT findings are heterogeneous and primarily include peribronchovascular thickening, nodules, ground-glass opacities and lymphadenopathy. There is no specific diagnostic test for IgG4-RD thoracic involvement, which may mimic malignancy or vasculitis. Therefore, a cautious approach is needed to make an accurate diagnosis: a search for extra-thoracic manifestations, elevated serum IgG4 levels, circulating levels of plasmablasts and pathologic evidence of disease is warranted. Although very suggestive, neither the presence of a polyclonal IgG4 lymphoplasmacytic infiltrate, storiform fibrosis or obliterative phlebitis are sufficient to confirm the histological diagnosis. Steroids are recommended as first-line therapy. Rituximab or disease-modifying antirheumatic drugs may be used in relapsed or rare cases of steroid-refractory disease. In this review, we summarize current knowledge regarding the pathophysiology, epidemiology, diagnostic modalities (clinical-biological-imaging-histopathology) and treatment of IgG4-RD thoracic involvement.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36437514 · DOI · PMC10100266
Current status of type 1 (IgG4-related) autoimmune pancreatitis [2]
Abstract reading summary — source excerpts
- Opening excerpt
- In 1995, Yoshida et al.
- Closing excerpt
- In this review, we discuss the current knowledge and recent advances relating to type 1 AIP.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (111 words)
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 neutrophil infiltration and granulocytic epithelial lesions (GEL). Recent research has clarified the clinical and pathophysiological aspects of type 1 AIP, which is more than type 2 among the Japanese population. However, many details remain unclear about the pathogenesis and progression of this disease. In this review, we discuss the current knowledge and recent advances relating to type 1 AIP.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35916965 · DOI · PMC9522839
IgG4 autoantibodies and autoantigens in the context of IgG4-autoimmune disease and IgG4-related disease [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Immunoglobulins are an essential part of the humoral immune response.
- Closing excerpt
- Lastly, we explore the current gaps in our knowledge and how these may be addressed.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (175 words)
Immunoglobulins are an essential part of the humoral immune response. IgG4 antibodies are the least prevalent subclass and have unique structural and functional properties. In this review, we discuss IgG4 class switch and B cell production. We review the importance of IgG4 antibodies in the context of allergic responses, helminth infections and malignancy. We discuss their anti-inflammatory and tolerogenic effects in allergen-specific immunotherapy, and ability to evade the immune system in parasitic infection and tumour cells. We then focus on the role of IgG4 autoantibodies and autoantigens in IgG4-autoimmune diseases and IgG4-related disease, highlighting important parallels and differences between them. In IgG4-autoimmune diseases, pathogenesis is based on a direct role of IgG4 antibodies binding to self-antigens and disturbing homeostasis. In IgG4-related disease, where affected organs are infiltrated with IgG4-expressing plasma cells, IgG4 antibodies may also directly target a number of self-antigens or be overexpressed as an epiphenomenon of the disease. These antigen-driven processes require critical T and B cell interaction. Lastly, we explore the current gaps in our knowledge and how these may be addressed.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38433835 · DOI · PMC10904653
Immunological Biomarkers to Assess Activity and Treatment Response in IgG4-Related Disease [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Background and Objectives: IgG4-related disease is a chronic fibro-inflammatory condition.
- Closing excerpt
- None of these biomarkers correlated with organ damage.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (267 words)
Background and Objectives: IgG4-related disease is a chronic fibro-inflammatory condition. Despite the development of classification and responder indexes, reliable biomarkers for disease activity and therapeutic monitoring remain limited. We evaluate the performance of a panel of biomarkers, including cytokine profiles, plasmablasts and conventional markers. Materials and Methods: We conducted a cross-sectional, single-center study, involving 35 patients diagnosed with IgG4-RD. Disease activity was evaluated using the IgG4-RD Responder Index (RI), Damage Index (DI) and clinical assessment. Laboratory evaluation included serum IgG4, total IgG, CRP, ESR, eosinophils, IgE, complement levels, and cytokine profiling via multiplex immunoassay. B cell subpopulations were analyzed by flow cytometry. Statistical analyses were performed using STATA/BE 17.0. Results: Patients with active disease (RI > 4 or clinical judgment) exhibited significantly higher levels of total IgG (p = 0.02), IgG4 (p = 0.01), and IL-5 (p = 0.03). PET-positive patients showed a Th1-skewed immune profile, with elevated IFN-γ/IL-4 (p p = 0.03), and increased eosinophils (p = 0.03). Clinician-assessed active disease was associated with higher total IgG levels (p = 0.01). Treatment-specific effects were observed: prednisone was associated with lower IgG4 and C3 levels. Notably, plasmablasts did not consistently correlate with clinical or imaging activity scores, possibly reflecting treatment status or B cell dynamics. Conclusions: This study demonstrates that cytokine ratios, particularly those involving IL-5, IL-13, IL-21, and IFN-γ, offer complementary information to traditional serological markers for IgG4-RD activity. While PET/CT-defined activity was best reflected by biomarkers of an IFN-γ-mediated pathway, the IgG4-RD RI demonstrated a stronger association with conventional humoral markers like serum IgG4 and total IgG. None of these biomarkers correlated with organ damage.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41752722 · DOI · PMC12942627
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease [5]
- Research article IgG4-related disease: an update on pathophysiology and implications for clinical care [6]
- Research article Advances in the diagnosis and management of IgG4 related disease [7]
- Research article British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis [8]
- Research article European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations [9]
- Research article Clinical Perspectives on IgG4-Related Disease and Its Classification [10]
References
- Muller R, Ebbo M, Habert P, Daniel L, Briantais A, Chanez P, et al.. Thoracic manifestations of IgG4-related disease. . 2023. PMID 36437514 · DOI · PMC10100266
- Uchida K, Okazaki K. Current status of type 1 (IgG4-related) autoimmune pancreatitis. . 2022. PMID 35916965 · DOI · PMC9522839
- Motta RV, Culver EL. IgG4 autoantibodies and autoantigens in the context of IgG4-autoimmune disease and IgG4-related disease. . 2024. PMID 38433835 · DOI · PMC10904653
- Moya-Alvarado P, Lopez-Gomez M, Martínez-Martinez L, Park HS, Leyva TF, Martín MC, et al.. Immunological Biomarkers to Assess Activity and Treatment Response in IgG4-Related Disease. . 2026. PMID 41752722 · DOI · PMC12942627
- Wallace ZS, Naden RP, Chari S, Choi HK, Della-Torre E, Dicaire JF, et al.. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 2020. PMID 31796497 · DOI
- Perugino CA, Stone JH. IgG4-related disease: an update on pathophysiology and implications for clinical care. Nat Rev Rheumatol. 2020. PMID 32939060 · DOI
- Lanzillotta M, Mancuso G, Della-Torre E. Advances in the diagnosis and management of IgG4 related disease. BMJ. 2020. PMID 32546500 · DOI
- Chapman MH, Thorburn D, Hirschfield GM, Webster GGJ, Rushbrook SM, Alexander G, et al.. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut. 2019. PMID 31154395 · DOI · PMC6691863
- Löhr JM, Beuers U, Vujasinovic M, Alvaro D, Frøkjær JB, Buttgereit F, et al.. European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations. United European Gastroenterol J. 2020. PMID 32552502 · DOI · PMC7437085
- Katz G, Stone JH. Clinical Perspectives on IgG4-Related Disease and Its Classification. Annu Rev Med. 2022. PMID 34669430 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.