sytemic lupus erythematosis
Post on 22-Feb-2016
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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 A core set was selected
Systemic Lupus - Definition
ACR Criteria for Lupus Diagnosis
• Malar Rash
• Discoid Rash
• Photo-sensitivity Rash
NonerosiveArthritis
PleurisyPericarditi
s
Renal Disorder(Lupus
Nephritis)
Seizures or Psychosis
• Leuko-penia
• Hemolytic anemia• Thrombo-
cytopenia
• Anti- nuclear Antibody (ANA)
• dsDNA• APL
Oral Ulcers
SKIN GI MUSCULO-SKELETAL
PULMONARY /CARDIAC RENAL NEUROLOGICAL HEMATOLOGIC IMMUNOLOGIC
Four at any time possible SLE DIAGNOSIS
Fatigue Rash Joint paint Pleurisy, pericarditis
Kidney disease Abnormal clotting Inflamed blood vessels Reduced blood cells
ACR Criteria Define a Heterogeneous Group of Disorders, Prevalence ~1/1000
Virus CancerCell
DyingCell
Normal Immune System Function: Recognition, Activation, Clearance, Reset
Cells of the immune system recognize the target, bind to it, become activated, and make antibodies against the target.
Target
Lymphocytes
When the target is a dying cell, the antibodies are autoantibodies
ANA DsDNA RO LA Anti-Smith Anti-RNP
LymphocyteTargetDying Cell
Killer
AntibodiesThe antibodies bind the target and complement.
Complement binds to transport cells, which clear the immune complex.
Dying Cell
Autoantibodies ANA Anti-DsDNA Anti-Smith Anti-RNP Ro/La
Killer
AntibodiesThe antibodies bind complement.
Complement binds to transport cells, which clear the immune complex.
Dying Cell
Autoantibodies ANA Anti-DsDNA Anti-Smith Anti-RNP Ro/La
Killer
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
If the immune system does not reset perfectly, immune cells may damage normal cells, and antibodies may bind to healthy tissue.
Dysregulation of the normal process of recognition, activation, clearance, and reset of the immune system
Leading to persistence of pathogenic (damaging) subsets of immune cells and proteins
SLE: Cause
Problem GeneToo many dying cells TNF, PARP
White cells too active or long-lived
Il-10, IL4, IFNg, and their receptors
Antibodies too abundant or sticky
HLA class 1Immunoglobulin chains
Too little complement C1Q, C2, C4
Inadequate transport Fc receptorsComplement receptors
Many different genetic variations lead to persistence of self-reactive cells and Abs
Emerging Approaches: Genetics
Emerging Approaches: Expression
Systemic Lupus:Treatment
Severe / Serious Flare Chronic Activity Remission
Patient’s Condition
Patient experiences increased disease activity that threatens
organs or well-being and requires immediate aggressive treatment
Patient experiences persistent activity that is not immediately
threatening to organ systems, but requires ongoing treatment to
control symptoms
Patient experiences minimal or no disease symptoms or signs
Primary Treatment
Goal
Achieve rapid control of inflammation and disease-
mediated dysfunction
Maintain control of disease with minimal toxicity
Maintain remission with minimal toxicity
Commonly Used
Treatments
High dose corticosteroids MMF Cyclophosphamide
Low to medium dose corticosteroids
MMF / AZA / MTX Belimumab Antimalarials
Low to medium dose corticosteroids
MMF / AZA / MTX Belimumab Antimalarials
Level of Disease Activity Controlled
High
Low
SLE: Current Treatment
Severe / Serious Flare Chronic Activity Remission
Unmet Need Faster, less toxicity, Less Damage
More complete, less toxicity, safe with
pregnancy Cure
Commonly Used
Treatments
High dose corticosteroids MMF Cyclophosphamide
Low to medium dose corticosteroids
MMF / AZA / MTX Belimumab Antimalarials
Low to medium dose corticosteroids
MMF / AZA / MTX Belimumab Antimalarials
Level of Disease Activity
Controlled
High
Low
SLE: Unmet Need
Targets for Emerging Therapies
Immune Dysfunction
• Genetic susceptibility
• Gender• Environmental
factorsoUV lighto Infection
Defective Regulatory
Circuits
DefectiveImmuneComplex
Clearance
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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