Autoimmune Diseases Overview

Autoimmune Diseases

• Autoimmune diseases are caused by the immune system attacking self-tissues.
• Important autoimmune diseases include rheumatoid arthritis, multiple sclerosis, type 1 diabetes, Graves' disease, and myasthenia gravis.
• The causes of many autoimmune diseases are not clear.
• Pathogenic antibodies and immune cells (T cells) are believed to contribute to immune damage.
• Autoimmune diseases are common, frequently affecting young people, and more prevalent in women.
• They are often chronic, long-term conditions with significant personal and socioeconomic burdens.
• Costs can be high, for example, $30,000/year medication for MS, plus lost wages, etc.
• Some autoimmune diseases can arise spontaneously or be induced by factors like drugs or rabies vaccines.
• Currently, there is no cure for most autoimmune diseases, but treatments exist with potential side effects.

Immune System Related Diseases

• Autoimmune diseases are a category of immune system-related disorders.
• Hypersensitivity disorders (allergies) are another category.
• Immunodeficiencies are also related to the immune system, making a person more susceptible to infections.
• And neoplasias (leukemia, lymphomas, and others) can affect the immune system, often negatively.

Treatment and Problems

• Glucocorticoids (e.g., Prednisolone) are used, but can cause side effects like hyperglycemia, skin changes, muscle loss, osteoporosis, and more.
• Mitoxantrone is a cancer drug used with potential side effects like nausea, vomiting, hair loss, and immunosuppression, and concerns around cardiomyopathy.
• TNF inhibitors (e.g., infliximab, adalimunab) can cause T-cell lymphomas and other opportunistic infections.
• Interferon beta can cause flu-like symptoms.
• Rituximab (anti-CD20 Ab) can create issues like cardiac arrest, acute renal failure, and various infections.
• Tysabri (anti-VLA-4) can cause progressive multifocal leukoencephalopathy (PML).
• Campath (Alemtuzumab) can lead to autoimmune thyroiditis.
• Fingolimod (FTY720) can potentially cause skin cancer and hemorrhagic encephalitis.

How Autoimmune Diseases Arise

• Molecular mimicry: Immune system mistakenly targeting microbial proteins similar to self-proteins.
• Failure of regulatory mechanisms: Lack of tolerance, insufficient regulatory T cells or regulatory B cells.

Genetic Bases of Autoimmune Diseases

• HLA (MHC) genes are strongly linked to many autoimmune diseases.
• Specific HLA class II alleles are linked to conditions like multiple sclerosis (HLA-DR2), rheumatoid arthritis (HLA-DR1, -DR4), and others.

Other Genes and Environmental Factors

• AIRE (Autoimmune regulator) is responsible for presenting self-antigens in the thymus, absence linked to autoimmune polyglandular syndrome.

• Foxp3 is linked to IPEX and ALPS syndromes, relating to regulatory T cell impairment and autoimmunity.

• Fas deficiency can lead to autoimmune lymphoproliferative syndrome.

• Certain infections like Campylobacter jejuni, Group A Streptococcus, and EBV are linked to autoimmune diseases.

• Environmental factors like smoking, high salt diet, and obesity are also potentially connected to autoimmune diseases.

Classification of Autoimmune Diseases

• Organ-specific autoimmune diseases involve attacking specific organs.
• Antibody-mediated diseases, like Grave's, are mediated by antibodies.
• Cell-mediated diseases, such as Multiple Sclerosis, are mediated by cells.

Graves' Disease (Basedow)

• Autoimmune hyperthyroidism, causing overactive thyroid gland. Also termed Diffuse Toxic Goiter or Basedow Disease.

Myasthenia Gravis (MG)

• Blocking antibodies against acetylcholine receptors in muscles lead to muscle weakness,.

Goodpasture's Syndrome

• "Destructive" autoantibodies against glomerular basement membrane that damage tissues, commonly lungs and kidneys.

Type 1 Diabetes Mellitus

• Autoimmune attack against insulin-producing beta cells in the pancreas.

Multiple Sclerosis (MS)

• Demyelination of the central nervous system (CNS) is characteristic.
• Remitting-relapsing or progressive disease.

Systemic Lupus Erythematosus (SLE)

• Systemic autoimmune disorder with varying symptoms and organ involvement, including skin "butterfly rash", kidney issues, and other problems..
  • Antinuclear antibodies (ANA) are characteristic (e.g., Anti-double stranded DNA antibodies).
  • Typically affects women more.

Rheumatoid Arthritis (RA)

• Chronic inflammatory disease of small joints, often with morning stiffness.
• Symptoms can include pain, swollen joints, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies (anti-CCP).
• Can cause long-term, severe joint deformities.

Patient Presentations (Specific cases included in the document)

Additional Notes (includes data, figures etc)

• The document includes information regarding a suspected diagnosis for a child, and patient presentations to the ER with other conditions.
• Various images, figures, and relevant diagnostic information are contained in the documents.