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Autoimmune Disorders01:29

Autoimmune Disorders

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Autoimmune diseases are a group of disorders in which the body's immune system mistakenly attacks its own cells, tissues, and organs. This results from an overactive immune response against substances and tissues normally present in the body. Let's delve into the concept and mechanism of autoimmune diseases from an immune system point of view, explore different causes and examples of such diseases, and discuss potential solutions.
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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.
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Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular...
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Type I Diabetes I: Introduction01:12

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Type 1 diabetes mellitus is a chronic metabolic disorder characterized by an absolute deficiency of insulin resulting from the autoimmune destruction of pancreatic β-cells. Although it can occur at any age, it is most commonly diagnosed in childhood, adolescence, or early adulthood. The loss of insulin production impairs cellular glucose uptake, resulting in persistent hyperglycemia and necessitating lifelong insulin therapy.Autoimmune Destruction of β-CellsThe hallmark of type 1...
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Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
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Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
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IgA deficiency and autoimmunity.

Karmtej Singh1, Christopher Chang, M Eric Gershwin

  • 1451 E. Health Sciences Drive, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, United States.

Autoimmunity Reviews
|October 26, 2013
PubMed
Summary
This summary is machine-generated.

Immunoglobulin A (IgA) deficiency impacts mucosal immunity and infection protection. Research explores its genetic links to autoimmunity and geographical variations, with ongoing studies on cytokine roles.

Keywords:
Autoimmune diseaseCombined variable immunodeficiency (CVID)IgAImmunodeficiencyImmunoglobulinsSelective IgA deficiency

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Area of Science:

  • Immunology
  • Genetics
  • Epidemiology

Background:

  • Immunoglobulin A (IgA) is crucial for mucosal immunity, tolerance, and infection defense, particularly in the respiratory and gastrointestinal tracts.
  • Current definitions of IgA deficiency rely on limited early studies.
  • IgA deficiency exhibits geographical variations, with higher incidence in Caucasians than Asians, and is associated with autoimmune diseases, allergies, and malignancies.

Purpose of the Study:

  • To review the epidemiology and known associations of Immunoglobulin A (IgA) deficiency.
  • To explore potential genetic linkages, including MHC and non-MHC associations, that may explain geoepidemiological diversity and co-occurrence with autoimmunity.
  • To investigate the underlying pathogenesis, potentially involving switched memory B cell dysfunction, and explore cytokine-driven IgA synthesis.

Main Methods:

  • Literature review of IgA deficiency epidemiology, genetic associations (MHC and non-MHC), and clinical co-morbidities.
  • Analysis of existing data on geographical incidence variations and associations with autoimmune diseases.
  • Discussion of proposed pathogenetic mechanisms and ongoing research into cytokine roles (IL21, CD40L, IL-4, IL10) in IgA synthesis.

Main Results:

  • IgA deficiency shows significant geographical incidence disparities.
  • Strong associations exist between IgA deficiency and autoimmune diseases, allergies, and malignancies.
  • Genetic associations, including the 8.1 haplotype, IFIH1, and CLEC16A, are implicated in IgA deficiency and autoimmunity.
  • Pathogenesis may involve impaired switched memory B cell function, leading to increased infections and autoimmunity.

Conclusions:

  • IgA deficiency is a complex condition with diverse geographical distribution and significant co-morbidities, particularly autoimmune diseases.
  • Genetic factors, including MHC and non-MHC loci, likely play a role in its pathogenesis and epidemiological variations.
  • Further research into B cell function and cytokine-mediated IgA synthesis is essential for understanding and potentially treating IgA deficiency.