IS Lecture --- Autoimmune Diseases

• Autoimmune diseases


  When the immune system fails to discriminate self from nonself, and attacks self antigens, leading to damage or destruction of cells and tissues
• Development of autoimmune diseases

  1. Genetic predisposition

  2. Triggered by external factors (pollution, stress, diet)

  3. Triggered by hormonal and environmental factors

  4. Autoantibodies formed initially without symptoms

  5. Damage progresses, leading to recognizable signs and symptoms
• Systemic autoimmune diseases


  • Affect many organs and tissues in the body
• Systemic Lupus Erythematosus (SLE)


  A disease of the connective tissue, expressed as a vasculitis (inflammation/swelling in blood vessels), an immune complex disease where autoantibodies attack the patient's own antigens
• SLE


  • Most common in female patients
  • Develops photosensitivity (sunlight exposure accentuates the erythematosus rash)
  • Most striking feature is the presence of anti-nuclear antibodies (ANA) in the serum
• Serologic test for ANA

  1. Indirect fluorescent antibody test

  2. Antinuclear antibody (ANA) visible method
• Fluorescence staining patterns


  • Homogenous (equal distribution in nucleoplasm)
  • Peripheral/Prim (found at the periphery of the nucleus; ring, membranous, shaggy/thready)
  • Speckled (mottled, "pepper dots"; found in the nucleoplasm, associated with anti-extractable nucleus antigens)
  • Nucleolar (reflects antibodies to nucleolar RNA)
• Anti-centromere antibody (ACA)


  • Highly selective for CREST variant of Scleroderma (Calcinosis cutis, Raynaud's Phenomenon, Esophageal Dysmotility, Sclerodactyly, Telangiectasia)
• Less common ANA patterns include mixed patterns (multiple antibodies present) and the antinuclear antibody (ANA) visible method (indirect immunoenzyme method)
• Riboflavin deficiency


  Indicated by cheilosis; due to the malabsorption of riboflavin rich food in the intestine due to scleroderma
• Raynaud's Phenomenon


  Purplish black signifies gangrenous necrosis (fingertips/nails); because of the vasospasm
• Reynaud's Phenomenon: The blood flow in the area is limited, oxygen & nutrients are decreased which leads to tissue death
• Similar with case of people with "frostbite"


  Tissue death is "irreversible"; there will be amputation
• ANA Patterns

  • Homogenous
  • Membranous
  • Speckled
  • Nucleolar
• Mixed ANA Patterns


  • There is membranous, homogenous, pepper dots, and nucleolar
  • There is multiple antibodies present
• ANTINUCLEAR ANTIBODY (ANA) VISIBLE METHOD


  • Indirect: antibody will be detected
  • Immuno: Ab is reagent
  • Enzyme: conjugated labeled
  • Same method but different in labeled
  • Same pattern but different color in pattern
• Principle: Indirect Immunoenzyme Method

  1. Hep2 cells (Nuclear Ags) + Px serum w/ ANA + AHG-with labeled Horseradish Peroxidase (HRP) + Stain (diaminobenzidine)

  2. (+) for ANA - brown cytoplasmic or nuclear stain
• Rheumatoid Arthritis


  An autoimmune disease causing chronic inflammation of the joints and periarticular
• Rheumatoid Arthritis is different from osteoarthritis or other type of arthritis
• Normal Joint


  • Has sufficient synovial fluid to prevent friction and to provide nutrients for the synovial sites
  • Synovial membrane is also intact
  • Cartilage is normal in the bones, tendons as well
• Osteoarthritis


  • The problem is on the cartilage
  • The cartilage is already thinned; both ends of the bones rubbing together causes pain and inflammation
  • Mechanical is the cause of inflammation
  • Most common among males
• Rheumatoid Arthritis


  • There is bone erosion, swelling because of infiltration of immunocompetent cells (WBCs)
  • There are deposits of immune complexes present in the synovial cavity
  • Immunological is the cause
  • Most common among females
• Rheumatoid Factor

  • Group of immunoglobulins that interact specifically with the Fc portion of IgG molecules (anti-antibodies)
  • Primarily, are of the IgM class
  • Also known as anti-antibodies; RF is an antibody which reacts with another antibody
  • IgM serves as the antibody which reacts at the Fc portion of IgG (serves as the target antigen)
• In the laboratory: RF is tested to diagnose RA. If the result is (-) RF but the clinical sign and symptoms are linked associated with RA, Physicians request Arthrocentesis (synovial fluid)
• There is high sensitivity of RF in the synovial fluid rather than in the serum
• RF is present, PMN, lymphocytes macrophage are present
• The presence of immune cells in the brain cavity can resolve in the release of cytokines, enzymes
• Release of cytokines, enzymes can trigger erosion of the bones; cause destruction of the joint cavity
• Infiltration of immune cells causes bone erosion and destruction of bones
• Immune complexes present because of RF attaching to human antibodies can also trigger inflammation reactions
• In RA, there are immune cells and antibodies involved
• Rheumatoid Factor Latex Test

  • Principle: Passive Agglutination
  • Reagent Ag: Human IgG
  • Antibody used: RF
  • Latex coated with albumin & denatured human IgG (serves as antigen) + Px serum w/ RF (Anti-IgG)
  • (+) Agglutination
• Ankylosing Spondylitis


  • A form of chronic inflammation of the spine and the sacroiliac joints
  • Ankylosing: complete cementing/hardening/fusion of the vertebrae causing inability to bend, immovable spinal cord
  • Spondylitis: Inflamed
  • Chronic inflammation in these areas causes pain and stiffness in and around the spine
  • Over time, chronic spinal inflammation (spondylitis) can lead to a complete cementing together (fusion) of the vertebrae, a process referred to as "ankylosis"
  • Ankylosis leads to loss of mobility of the spine
  • The autoimmune disease with the highest criteria for HLA-disease relationship; associated w/ HLA Ag B-27
  • More common in male patients
• Progressive Systemic Sclerosis: Scleroderma


  • Chronic disease of the connective tissue characterized by diffuse fibrosis involving the skin and several internal organs
  • Raynaud's phenomenon: pain in the extremities when exposed to cold (VASOSPASM)
• Sjoren's Syndrome


  • Most often occurs secondary to RA, SCLERODERMA, SLE
  • Manifestations: Dry eyes: KERATOCONJUNCTIVITIS SICA, Dry mouth: XEROSTOMIA
• Organ-Specific Autoimmune Diseases

  • Goodpasture's syndrome: Anti-Glomerular Basement Membrane (Kidneys)
  • Pernicious Anemia: Anti-Intrinsic Factor, Anti-Parietal cells (Stomach)
  • Multiple Sclerosis: Anti-Myelin sheath (Myelin Sheath of Nerve Cells (Axon))
  • IDDM (Type 1 Diabetes): Anti-Islet cells (Anti-Beta cells) (Pancreas)
  • Grave's Dse: Anti-Thyroglobulin (Thyroid gland)
  • Hashimotos's thyroiditis: Anti-LATS (Anti-Long Acting Thyroid Stimulating Cells) (Thyroid gland)
  • Wegener's granulomatosus: ANCA (Anti-Neutrophil Cytoplasmic Antibodies) (Kidneys)
  • Myasthenia gravis: Anti-Acetylcholine receptors (Muscles)
• Two Important Anti-Cytoplasmic Antibodies

  • Anti-Smooth Muscle Antibody (anti-SMA): High titer is strongly suggestive of Chronic Active Hepatitis
  • Anti-Mitochondrial Antibody (AMA): Useful marker for Primary Biliary Cirrhosis
• Anti-Phospholipid Abs (APA)


  • Synonymous with Anticardiolipin Antibody/Lupus Anticoagulant
  • Also with Lupus Anticoagulant, an anti-phospholipid that causes prolongation of Activated Partial Thromboplastin Time (ATTP). Affected pathways are intrinsic and common pathways of coagulation