Autoimmune Diseases Overview

Autoimmune Diseases

• Autoimmune diseases are caused by the immune system attacking healthy tissues.
• Examples include rheumatoid arthritis, multiple sclerosis, type 1 diabetes, Graves' disease, and myasthenia gravis
• The cause of most autoimmune diseases isn't clear.
• Pathogenic antibodies and immune cells (T cells) contribute to immune damage.

Immune System Related Diseases

• Autoimmune diseases
• Hypersensitivity disorders (allergies)
• Immunodeficiencies
• Neoplasia (leukemias, lymphomas, others)

Autoimmune Diseases: Notable Facts

• Estimated 8 million people in the US alone have autoimmune diseases.
• They often affect young individuals.
• Autoimmune diseases are typically chronic.
• Personal and socioeconomic burdens are often significant. (e.g., 30,000/yearmedication,30,000/year medication, 30,000/yearmedication,30,000 lost wages for multiple sclerosis alone, at least $24 billion dollars/year in total cost to the USA)
• Some diseases can be induced by drugs or vaccines.
• There is currently no cure for most autoimmune diseases, but treatments exist with side effects.

Treatments and Their Problems

• Glucocorticoids (e.g., Prednisolone): Immunosuppression, hyperglycemia, skin issues, muscle weakness, osteoporosis, weight gain, glaucoma, cataracts, euphoria/psychosis
• Mitoxantrone: A cancer drug. Side effects include nausea, vomiting, hair loss, immunosuppression, and cardiomyopathy
• TNF inhibitors (e.g., infliximab, adalimumab): Can cause T cell lymphomas, opportunistic infections, or TB.
• Rituximab: Cardiac arrest, acute renal failure, infections, progressive multifocal leukoencephalopathy (PML), and pulmonary problems are possible side effects.
• Tysabri: Progressive multifocal leukoencephalopathy (PML) is a potential side effect.
• Campath: Autoimmune thyroiditis is a potential side effect.
• Fingolimod: Skin cancer and hemorrhagic encephalitis are potential side effects.

Immunological Facts

• The immune system responds to a vast range of antigens.
• Autoreactive B and T cells exist even in healthy individuals.
• Some autoantibodies might be found in healthy individuals.
• Some T and B cells recognize self-antigens, with the potential to attack healthy tissue.
• Autoimmunity is an immune response against self-tissues.
• Autoimmune disease is an autoimmune response resulting in tissue damage.

How Autoimmune Diseases Arise

• Molecular mimicry: Mimicry of self proteins by microbes to trigger an unwanted immune response. Examples include rheumatic fever and Guillain-Barré syndrome.
• Failure of regulatory mechanisms: A breakdown in mechanisms that prevent the immune system from attacking self-tissues
• Access to "forbidden sites": Normally sequestered tissues can become accessible to immune cells due to inflammation.
• Genetic and environmental factors: Inherited factors and experiences, including infections, diet, and microbiome all contribute to autoimmune disorders

HLA (MHC) in Autoimmune Diseases

• HLA (MHC Class II) is a strong genetic factor in autoimmune diseases.
• Specific HLA types have connections with certain autoimmune diseases. The example cited shows associations with multiple sclerosis, rheumatoid arthritis, celiac disease, and type 1 diabetes.
• Genetic factors contribute to the development and incidence of autoimmune conditions

Other Genes and Environmental Factors

• AIRE: Failure to present self-antigens in the thymus can lead to autoimmune polyglandular syndrome.
• Foxp3: Mutations in this gene can cause immune dysregulation in IPEX syndrome.
• Fas: A deficiency of this death receptor is linked to autoimmune lymphoproliferative syndrome (ALPS).
• Polymorphisms of TNF or TNF receptor genes: These genes' variations correlate with autoimmune disease risks
• CTLA-4 and IL-7R are other gene variations associated with autoimmune conditions
• Certain infections correlate with specific autoimmune diseases: Example is campylobacter jejuni and Guilllian-Barré syndrome
• Other factors include Group A Streptococcus, EBV, Coxsackie, and gut microbiome

Classification of Autoimmune Diseases

• Organ-specific: Affecting specific organs
  • Antibody-mediated: Grave's disease, myasthenia gravis, Goodpasture's syndrome
  • Cell-mediated: Multiple sclerosis, type 1 diabetes
• Systemic: Affecting multiple organs
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
• Note: Antibodies and immune cells often contribute to autoimmune pathology.

Diagnosis, Graves' Disease

• Symptoms and signs can be used as diagnostic clues.
• Thyroid hormone, thyroid-stimulating hormone, and thyroid-stimulating antibodies are used for diagnostic measures

Diagnoses: Graves' Disease/Basedow Disease

• Autoimmune hyperthyroidism that is induced through immune overactivity of thyroid glands.
• Also known as diffuse toxic goiter or Basedow disease

Diagnoses: Myasthenia Gravis (MG)

• Acetylcholine receptor antibodies block acetylcholine from binding, decreasing muscle activation.
• Patients show progressive muscle weakness.
• Myasthenic crisis is characterized by severe exacerbation of MG
• Can be triggered by infection
• Cholinergic Crisis is an adverse consequence of medical treatment

Goodpasture's Syndrome

• Characterized by lung and kidney damage.
• Presents as coughing up blood (hemoptysis), shortness of breath, kidney problems (rapidly progressive glomerulonephritis, hematuria, proteinuria, high blood pressure).
• Diagnosis involves kidney biopsy, tests for anti-glomerular basement membrane antibodies and related tests.
• Treatment involves immune suppression and corticosteroids.

Type 1 Diabetes Mellitus (IDDM)

• Autoimmune destruction of insulin-producing beta cells in the pancreas.
• Leads to high blood sugar.
• Characterized by excessive urination, excessive thirst, and increased appetite.
• Diagnosis involves testing blood glucose levels (fasting sugar, random, 2-hour glucose tolerance test; HbA1c).
• Treatment involves insulin therapy.
• Symptoms include hyperglycemia, excessive urination, weight loss, and increased appetite.
• Untreated, can lead to diabetic ketoacidosis, coma, dehydration

Systemic Lupus Erythematosus (SLE)

• Autoimmune disease affecting various tissues and organs in the body.
• Symptoms can be nonspecific including fever, fatigue, malaise, joint pain. Facial "butterfly" rash.
• Common, but difficult to accurately diagnose.
• Diagnosis involved comprehensive investigations including tests for antinuclear antibodies (ANA), anti-double stranded DNA (dsDNA) antibodies, and other antibodies.
• Treatment involves corticosteroids and immunosuppressants.

Rheumatoid Arthritis (RA)

• Chronic inflammatory disease targeting small joints.
• Can damage various tissues.
• Diagnostic criteria might include morning stiffness, painful joints (particularly in hands), and swollen joints.
• Key indicators include rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies.
• Treatment options involve immunosuppressants, anti-inflammatory drugs, and physical therapy.

Explore the world of autoimmune diseases with this quiz. Learn about common conditions such as rheumatoid arthritis and multiple sclerosis, as well as the complexities of the immune response. This quiz also covers the socioeconomic impacts and notable facts surrounding these chronic conditions.