Related Experiment Video
Updated: Jun 18, 2025
Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
Multiorgan involvement and circulating IgG1 predict hypocomplementaemia in IgG4-related disease
Guy Katz1,2, Cory Perugino3,2,4, Zachary S Wallace3,2
1Massachusetts General Hospital Division of Rheumatology Allergy and Immunology, Boston, Massachusetts, USA gkatz@mgh.harvard.edu.
Insights
Hypocomplementaemia, common in IgG4-related disease (IgG4-RD), is linked to disease extent, particularly lymph node and lung involvement. IgG1 levels, not IgG4, correlate with this complement deficiency, suggesting complement activation in IgG4-RD.
Area of Science:
- Immunology
- Rheumatology
- Pathophysiology
Background:
- Hypocomplementaemia is frequently observed in patients diagnosed with IgG4-related disease (IgG4-RD).
- Understanding the clinical features and underlying mechanisms associated with hypocomplementaemia in IgG4-RD is crucial for disease management.
Purpose of the Study:
- To identify specific IgG4-related disease (IgG4-RD) features associated with hypocomplementaemia.
- To explore the mechanisms of complement activation in the context of IgG4-RD.
Main Methods:
- A single-centre cross-sectional study was conducted involving 279 patients meeting IgG4-RD classification criteria.
- Unadjusted and multivariable-adjusted logistic regression analyses were employed to identify factors linked to hypocomplementaemia.
Main Results:
- Hypocomplementaemia was present in 32% of patients.
- Initially, involvement of multiple organs, lymph nodes, lungs, pancreas, liver, and kidneys showed associations with hypocomplementaemia.
- After adjustment, lymph node and lung involvement remained significantly associated, while renal involvement was attenuated. Fibrotic manifestations and lacrimal gland involvement showed inverse associations.
- Hypocomplementaemia correlated with higher concentrations of all IgG subclasses and IgE. Crucially, only IgG1, not IgG4, independently correlated with hypocomplementaemia after adjustment.
Conclusions:
- Hypocomplementaemia in IgG4-RD is associated with the overall extent of the disease and is not exclusive to renal involvement.
- The study highlights a significant independent correlation between IgG1 levels and hypocomplementaemia in IgG4-RD, challenging the role of IgG4.
- These findings suggest that complement activation plays a role in the pathophysiology of IgG4-related disease.
Objectives:
Hypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease.
Methods:
We performed a single-centre cross-sectional study of 279 patients who fulfilled the IgG4-RD classification criteria, using unadjusted and multivariable-adjusted logistic regression to identify factors associated with hypocomplementaemia.
Results:
Hypocomplementaemia was observed in 90 (32%) patients. In the unadjusted model, the number of organs involved (OR 1.42, 95% CI 1.23 to 1.63) and involvement of the lymph nodes (OR 3.87, 95% CI 2.19 to 6.86), lungs (OR 3.81, 95% CI 2.10 to 6.89), pancreas (OR 1.66, 95% CI 1.001 to 2.76), liver (OR 2.73, 95% CI 1.17 to 6.36) and kidneys (OR 2.48, 95% CI 1.47 to 4.18) were each associated with hypocomplementaemia. After adjusting for age, sex and number of organs involved, only lymph node (OR 2.59, 95% CI 1.36 to 4.91) and lung (OR 2.56, 95% CI 1.35 to 4.89) involvement remained associated with hypocomplementaemia while the association with renal involvement was attenuated (OR 1.6, 95% CI 0.92 to 2.98). Fibrotic disease manifestations (OR 0.43, 95% CI 0.21 to 0.87) and lacrimal gland involvement (OR 0.53, 95% CI 0.28 to 0.999) were inversely associated with hypocomplementaemia in the adjusted analysis. Hypocomplementaemia was associated with higher concentrations of all IgG subclasses and IgE (all p<0.05). After adjusting for serum IgG1 and IgG3, only IgG1 but not IgG4 remained strongly associated with hypocomplementaemia.
Conclusions:
Hypocomplementaemia in IgG4-RD is not unique to patients with renal involvement and may reflect the extent of disease. IgG1 independently correlates with hypocomplementaemia in IgG4-RD, but IgG4 does not. Complement activation is likely involved in IgG4-RD pathophysiology.
Related Concept Videos
01:15Transcytosis of IgG
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
01:36Humoral Immune Responses
01:30Hypersensitivities
Types of Hypersensitivities
Hypersensitivity reactions are categorized into four types: Type 1, Type 2, Type 3, and Type 4. Each type has a distinct mechanism...
01:17Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...