Fulminant Viral Hepatitis in Two Siblings with Inherited IL-10RB Deficiency
Cecilia B Korol1,2, Serkan Belkaya3,4, Fahad Alsohime5
1Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
Journal of Clinical Immunology
|October 29, 2022
Summary
Inherited IL-10 receptor beta (IL-10RB) deficiency can cause severe hepatitis A virus (HAV) infections. This genetic condition impairs immune responses, potentially leading to fulminant viral hepatitis (FVH) and inflammatory bowel disease (IBD).
Area of Science:
- Immunology
- Genetics
- Hepatology
Background:
- Fulminant viral hepatitis (FVH) from Hepatitis A Virus (HAV) is rare but severe.
- Inherited Interleukin-18 Binding Protein (IL-18BP) deficiency is a known genetic cause of FVH.
- Early-onset inflammatory bowel disease (EOIBD) can co-occur with FVH.
Purpose of the Study:
- Investigate the genetic basis of FVH in siblings with EOIBD.
- Determine the functional impact of IL-10RB variants on cellular responses.
- Elucidate the molecular mechanisms linking IL-10RB deficiency to FVH.
Main Methods:
- Genetic analysis of siblings with EOIBD and FVH.
- Cellular assays to assess responses to IL-10, IL-22, IL-26, and Interferon-lambda (IFN-λ).
- Overexpression studies and analysis of homozygous cells for IL-10RB variants.
Main Results:
- Identified homozygous W100G variant in IL10RB in affected siblings.
- Demonstrated that IL-10RB variants disrupt cellular responses to IL-10, IL-22, IL-26, and IFN-λ.
- Showed impaired IL-10 signaling by W100G variant, potentially leading to excessive IFN-γ activity.
Conclusions:
- Inherited IL-10RB deficiency predisposes individuals to FVH, possibly via dysregulated IFN-γ.
- IL-10RB deficiency may contribute to both FVH and EOIBD.
- Recommend HAV vaccination for patients with IL-10RB, IL-10, or IL-10RA deficiencies.
Related Concept Videos
01:25Immunodeficiency Diseases
1.2K
Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency...
There are three main causes of immunodeficiency...
1.2K
01:29Immune Response Against Viral Pathogens
881
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
881
01:24T Cell Types and Functions
1.3K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.3K