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 ID: 495168
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Sytemic Lupus Erythematosis
The New Understanding:
Complexity and Promise
Jan L Hillson MDSlide2
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 SLEThese lists were comparedA core set was selected
Systemic Lupus - DefinitionSlide3
ACR Criteria for Lupus Diagnosis
Malar Rash
Discoid Rash
Photo-sensitivity Rash
NonerosiveArthritis
Pleurisy
Pericarditis
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 DIAGNOSISSlide4
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 ~1/1000Slide5
Virus
Cancer
Cell
Dying
Cell
Normal Immune System Function: Recognition, Activation, Clearance, ResetSlide6
Cells of the immune system recognize the target, bind to it, become activated, and make antibodies against the target.
Target
LymphocytesSlide7
When the target is a dying cell, the antibodies are autoantibodies
ANA
DsDNA
RO
LA
Anti-Smith
Anti-RNP
Lymphocyte
Target
Dying CellSlide8
Killer
Antibodies
The 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/LaSlide9
Killer
Antibodies
The antibodies bind complement.
Complement binds to transport cells, which clear the immune complex.
Dying Cell
Autoantibodies
ANA
Anti-DsDNA
Anti-Smith
Anti-RNP
Ro/LaSlide10
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 Slide11
Killer
If the immune system does not reset perfectly, immune cells may damage normal cells, and antibodies may bind to healthy tissue.Slide12
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: CauseSlide13
Problem
Gene
Too many dying cells
TNF, PARP
White cells too active or long-lived
Il-10, IL4, IFN
g
, and their receptors
Antibodies too abundant or sticky
HLA class 1
Immunoglobulin chains
Too little complementC1Q, C2, C4
Inadequate transport
Fc receptorsComplement receptors
Many different genetic variations lead to persistence of self-reactive cells and AbsSlide14
Emerging Approaches: GeneticsSlide15
Emerging Approaches: ExpressionSlide16
Systemic Lupus:
TreatmentSlide17
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
GoalAchieve rapid control of inflammation and disease-mediated dysfunction
Maintain control of disease with minimal toxicity
Maintain remission with minimal toxicityCommonly Used TreatmentsHigh dose corticosteroids
MMFCyclophosphamide
Low to medium dose corticosteroidsMMF / AZA / MTXBelimumabAntimalarials
Low to medium dose corticosteroids
MMF / AZA / MTXBelimumabAntimalarials
Level of Disease Activity
Controlled
High
Low
SLE: Current TreatmentSlide18
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 corticosteroidsMMF
CyclophosphamideLow to medium dose corticosteroidsMMF / AZA / MTXBelimumab
Antimalarials
Low to medium dose corticosteroidsMMF / AZA / MTXBelimumabAntimalarials
Level of Disease Activity
Controlled
High
Low
SLE: Unmet NeedSlide19
Targets for Emerging Therapies
Immune
Dysfunction
Genetic susceptibility
Gender
Environmental factors
UV light
Infection
Defective
Regulatory
Circuits
DefectiveImmuneComplexClearanceSlide20
Advocate for funding for research
Participate in lupus registries
In consultation with your physician, consider whether clinical trials are right for youUnderstand and carefully follow your personal treatment planMaintain knowledge, fitness, and participation
Systemic Lupus – What Can We Do?