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Sytemic Lupus Erythematosis

Sytemic Lupus Erythematosis. The New Understanding: Complexity and Promise Jan L Hillson MD. Gold standard is agreement among specialists To create the ACR criteria Several specialists made lists of all the features seen in the patients they say have SLE These lists were compared

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Sytemic Lupus Erythematosis

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  1. Sytemic Lupus Erythematosis The New Understanding: Complexity and Promise Jan L Hillson MD

  2. Gold standard is agreement among specialists To create the ACR criteria Several specialists made lists of all the features seen in the patients they say have SLE These lists were compared A core set was selected Systemic Lupus - Definition

  3. ACR Criteria for Lupus Diagnosis SKIN GI MUSCULO-SKELETAL PULMONARY /CARDIAC HEMATOLOGIC IMMUNOLOGIC RENAL NEUROLOGICAL • Malar Rash • Discoid Rash • Photo-sensitivity Rash Oral Ulcers NonerosiveArthritis Pleurisy Pericarditis Renal Disorder (Lupus Nephritis) Seizures or Psychosis • Leuko-penia • Hemolytic • anemia • Thrombo-cytopenia • Anti- nuclear Antibody (ANA) • dsDNA • APL Four at any time  possible SLE DIAGNOSIS

  4. ACR Criteria Define a Heterogeneous Group of Disorders, Prevalence ~1/1000 • Fatigue • Rash • Joint paint • Pleurisy, pericarditis • Kidney disease • Abnormal clotting • Inflamed blood vessels • Reduced blood cells

  5. Normal Immune System Function: Recognition, Activation, Clearance, Reset Virus Cancer Cell Dying Cell

  6. Cells of the immune system recognize the target, bind to it, become activated, and make antibodies against the target. Target Lymphocytes

  7. When the target is a dying cell, the antibodies are autoantibodies ANA DsDNA RO LA Anti-Smith Anti-RNP Lymphocyte Target Dying Cell

  8. Dying Cell The antibodies bind the target and complement.Complement binds to transport cells, which clear the immune complex. Antibodies Killer Autoantibodies ANA Anti-DsDNA Anti-Smith Anti-RNP Ro/La

  9. Dying Cell The antibodies bind complement.Complement binds to transport cells, which clear the immune complex. Antibodies Killer Autoantibodies ANA Anti-DsDNA Anti-Smith Anti-RNP Ro/La

  10. The virus, dead cell, or cancer cell is cleared.The immune system resets to a resting state, but keeps the memory of how to respond Killer

  11. If the immune system does not reset perfectly, immune cells may damage normal cells, and antibodies may bind to healthy tissue. Killer

  12. SLE: Cause Dysregulation of the normal process of recognition, activation, clearance, and reset of the immune systemLeading to persistence of pathogenic (damaging) subsets of immune cells and proteins

  13. Many different genetic variations lead to persistence of self-reactive cells and Abs

  14. Emerging Approaches: Genetics

  15. Emerging Approaches: Expression

  16. Systemic Lupus:Treatment

  17. SLE: Current Treatment High Controlled Low

  18. SLE: Unmet Need High Controlled Low

  19. Targets for Emerging Therapies Immune Dysfunction Defective Regulatory Circuits • Genetic susceptibility • Gender • Environmental factors • UV light • Infection Defective Immune Complex Clearance

  20. Advocate for funding for research Participate in lupus registries In consultation with your physician, consider whether clinical trials are right for you Understand and carefully follow your personal treatment plan Maintain knowledge, fitness, and participation Systemic Lupus – What Can We Do?

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