Primary immunodeficiencies: novel genes and unusual presentations
Luigi D Notarangelo1, Gulbu Uzel1, V Koneti Rao1
1Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Hematology. American Society of Hematology. Education Program
|December 7, 2019
Summary
Genomic advances reveal primary immune deficiencies (PIDs) beyond infections, with immune dysregulation being a key feature. Monogenic PIDs should be suspected in children with prolonged, multi-lineage autoimmune cytopenias, enabling targeted treatments.
Area of Science:
- Immunology
- Genetics
- Genomics
Background:
- Genomic advancements are expanding the understanding of primary immune deficiencies (PIDs).
- Traditionally, PIDs were defined by susceptibility to infections.
- Increasingly, immune dysregulation is recognized as a significant PID phenotype.
Observation:
- Distinct clinical presentations arise from different variants within the same gene.
- Autoimmune cytopenias in childhood, persistent for over a year and affecting multiple cell types, suggest monogenic PIDs.
- These findings highlight a shift in PID classification.
Findings:
- Immune dysregulation, including autoimmune cytopenias, is a frequent and sometimes primary manifestation of PIDs.
- Pathogenic variants in novel genes are continually identified, broadening the PID spectrum.
- Genetic analysis is crucial for diagnosing these complex cases.
Implications:
- Identifying the molecular basis of PIDs with immune dysregulation can lead to targeted therapies.
- Early suspicion of monogenic PIDs in specific autoimmune conditions is vital for timely diagnosis.
- Further research into PID mechanisms can improve patient outcomes and management strategies.
Related Concept Videos
01:25Immunodeficiency Diseases
1.8K
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...
1.8K
01:20Special Features of Adaptive Immunity
2.8K
The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
2.8K
01:43Sex-linked Disorders
108.0K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
108.0K
01:23Cystic Fibrosis: Pathogenesis
670
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
670
01:22Development of Immunocompetence
718
The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
718
01:26Antigens Involved in Adaptive Immunity
1.2K
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
1.2K