FINALS LAB

• Autoimmune disease


  Conditions in which damage to organs or tissues results from the presence of autoantibody or autoreactive cells
• Mechanisms that contribute to autoimmunity


  • Release of sequestered antigens
  • Molecular mimicry
  • Polyclonal B cell activation
  • MHC genes
• Release of sequestered antigens


  Antigens that are protected from encountering the circulation are not exposed to potentially reactive lymphocytes
• Molecular mimicry


  Many individual viral or bacterial agents contain antigens that closely resemble self antigens. Exposure to such foreign antigens may trigger antibody production that in turn reacts with similar self antigens
• Polyclonal B cell activation


  B cell defects include the abnormal expression or function of key signaling molecules, dysregulation of cytokines, and changes in B cell developmental subsets
• MHC genes contribute to autoimmunity
• Rheumatoid arthritis

  Chronic systemic inflammatory disease primarily affecting the joints, but can affect heart, lung and blood vessels. Immune complexes form and activate complement and the inflammatory response. Enzymatic destruction of cartilage is followed by abnormal growth of synovial cells, results in the formation of a pannus layer
• The three major symptoms of arthritis


  • Joint pain
  • Inflammation
  • Stiffness

  
• RA has been associated with more than 30 genetic regions of our DNA
• Patients who have

  • HLA-DRB1 alleles
  • PTPN22 gene polymorphisms
• Rheumatoid factor (RF)


  Autoantibody that is usually IgM and reacts with the Fc portion of IgG
• Approximately 70% to 90% test positive for RF
• Anti-CCP is a good marker for early diagnosis of RA, performed by ELISA
• Specificity of anti-CCP is 91% to 93%
• Combination of RF and anti-CCP has a specificity of 98% to 100% for an accurate diagnosis of RA
• Criteria for diagnosis of RA

  • Joint pain, stiffness and swelling for more than 6 weeks
  • Swelling affecting 3 to 4 different joints or more
  • Morning stiffness lasting longer than 30 minutes
  • Symmetrical symptoms affecting both sides of the body
  • Swelling and pain affecting the wrists, hands and finger joints
  • Subcutaneous nodules
  • Positive Anti-CCP
  • Elevated ESR and CRP
  • Positive test for rheumatoid factor
  • X-ray evidence of joint erosion

  
• Rheumatoid factor (RF)


  IgM autoantibody directed against the Fc portion of the IgG molecule, it is an anti-antibody
• RF is not specific for RA, found in other diseases
• LATEX AGGLUTINATION TESTS for RF


  Good for 70 to 90% of RA cases
• ELISA, chemiluminescence or nephelometry for RF have increased specificity
• Anti-CCP is a good marker for early disease
• Goal of RA treatment


  Achieve lowest level of disease, remission if possible. Minimize joint damage
• RA treatments


  • Rest
  • Non-steroidal anti-inflammatory drugs (NSAIDs) to control swelling and pain
  • Methotrexate to inhibit adenosine metabolism and T-cell activation
  • Slow acting anti-rheumatic drugs (with side effects)
  • Joint replacement
• Substantial functional loss seen in 50% of RA patients within 5 years
• RF Latex test

  Based on an immunologic reaction between the RF, the test serum and the corresponding human IgG bound to polystyrene latex particles. When test serum containing rheumatoid factors is mixed with the RF Latex reagent, visible agglutination occurs
• RF Latex reagent


  • Suspension of latex particles sensitized with specially prepared human IgG in glycine saline buffer
  • RF Positive control serum
  • RF Negative control serum
  • Glycine Concentrate (20X) to be diluted 1:20 with purified water (for quantitative test)
• Interpretation of RF Latex test

  A negative (normal) result means little or no rheumatoid factor in the blood, but doesn't rule out rheumatoid arthritis. A positive (abnormal) result means a higher level of rheumatoid factor was found, but doesn't always mean rheumatoid factors are causing symptoms
• Conditions where RF may be present


  • Scleroderma
  • Still's disease
  • Sjögren's syndrome
  • SLE
• Causes of false positive RF Latex test


  • Lipemic, hemolyzed, or heavily contaminated serum specimens
  • Reaction time longer than 3 minutes (drying effect)
  • SLE, Sjögren's syndrome, syphilis, and hepatitis
  • Rheumatic fever, osteoarthritis, tuberculosis, cancer, some diseases of viral origin, osteoarthrosis, arthritis type undetermined, myositis, and polymyalgia rheumatic
  • Aging
• Systemic lupus erythematosus (SLE)

  Classic model of autoimmune disease
• Different forms of lupus


  • Discoid (cutaneous lupus, limited to skin)
  • Systemic
  • Drug induced
  • Neonatal lupus
• Drug-induced lupus


  Occurs after use of certain medications like hydralazine hydrochloride, procainamide hydrochloride, anticonvulsants, and miscellaneous drugs
• Factors causing drug-induced lupus


  • Rate of drug metabolism
  • Drug influence on immune regulation
  • Genetic composition of the host
• Drugs that can produce clinical and serologic features of SLE


  • Antiarrhythmics: Procainamide hydrochloride
  • Anticonvulsants: Phenytoin
  • Antihypertensives: Hydralazine hydrochloride
  • Miscellaneous: Chlorpromazine, Isoniazid, Penicillin, Sulfonamides
• Neonatal lupus

  Acquired from the passage of maternal autoantibodies (anti-Ro/SS-A or anti-La/SS-B). Can affect the skin, heart and blood of the fetus or newborn. Appears within first several weeks of life and persist about 6 months before disappearing. Not a systemic lupus.
• Systemic lupus erythematosus (SLE)


  The cause is idiopathic or unknown. Primary defect in the regulation of the immune system is important in the pathogenesis of the disease.
• Factors influencing SLE

  • Hormonal influences (more common in women)
  • Genetic predisposition
  • Environmental factors (UV light, bacterial and viral infections)
• SLE occurs more frequently in women than in men, 10-15 times
• SLE is more common in black women, 1 in 245
• Etiology of SLE


  Idiopathic cause, primary defect in the regulation of the immune system, genetic predisposition, hormones and environmental factors may trigger the disease