Autoimmunity Flashcards
SLE common mutations
HLA-DR2 or DR3
Effect of estradiol on SLE
Less apoptosis of autoreactive B cells
Increase: IL-1, VCAM
SLE pathogenesis
UV/damage —> stress, ROS —> apoptosis —> inadequate clearance = NUCLEAR ANTIGENS
Defective self-tolerance —> ANAs —> immunocomplexes —> inflammation
SLE hypersensitivity
Type III
Endosomal TLR effect in SLE
B cells produce more ANAs —> DCs —> IFNa —> more response
Antibody types in SLE (4)
- ANAs
- Anti-smith vs ribonucleoproteins
- Anti-dsDNA (active disease)
- Anti-phospholipid
Anti-phospholipid antibodies types (3) and effect
- Anti-cardiolipin (also in syphilis)
- Lupus anticoagulant vs prothrombin
- Anti-b2 glycoprotein 1
HYPERCOAGULATIVE
DIAGNOSTIC antibodies in SLE
Smith and dsDNA
ANAs are hypersensitivity type III, what about the other antibodies in SLE?
Type II
Diagnostic criteria for SLE (11)
SOAP BRAIN MD
- Serositis: pleuritis, pericarditis
- Oral/nasal ulcers
- Arthritis >2 joints, no deformities
- Photosensitivity
- Blood: all low
- Renal: proteinuria, casts
- ANAs
- Immunologic: dsDNA, Sm
- Neurologic - seizures and psychosis
- MALAR rash
- DISCOID rash
Complex responsible for thrombus in SLE
Phospholipid b2 glycoprotein I complex
Virchow’s triad
- Venous stasis
- Endothelial damage
- Procoagulative state
SLE lab findings (not typically done)
- Low C3 and C4
- High ESR, CRP
- CBC all low
- High BUN, creatinine
- Electrolyte abnormalities
- RPR and VDRL positive
Nephritis in SLE
Diffuse proliferative glomerulonephritis
SLE treatment
- Glucocorticoids —> Cushings
- Immunosuppressants when severe
- Hydroxychloroquine
RA gene mutation
HLA - DRB1
RA pathogenesis
Damage —> citrulination or carbamylation = neoantigens
—> immune complexes —> deposit in synovial membrane —> activate osteoclasts = erosive
RA triggers (3)
Cigarette
HLA-DRB1
Infections: P.gingivalis, Prevotella (GI)
Autoantibodies in RA
ACPA
RF - target IgG
Fibroblast-like synoviocytes function in RA
Make MMP13 —> adheres to and invades cartilage
RA stages
Preclinical: ACPA, RF, cytokines
10 years
Early RA: CD4+, MQ, stromal cell activation, MMP line cavity
Established RA: MQ and fibroblasts
Synovium in RA
Synoviocytes and FLS expand —> IL-1, IL-6, TNF, MMP, PG, leukotrienes, microRNA
Fill with fibroblasts, adipocytes, vessels, immune cells
Joint damage in RA
MQ, neutrophils, mast cells —> cytokines and MMPs
MMPs: collagenases, stromelysins destroy cartilage
RA clinical manifestations (7)
- Peripheral and small proximal joints
- C1&C2
- Morning rigidity
- Symmetric, polyarticular
- Erosive
- 4 ORs: calor, tumor,
- Vasculitis
Deviations in RA
Cubital in wrist
Boutonniere/Ojal: fold, extend
Swan: extend, fold
Z thumb
Rx in RA (3)
- Less articular space
- Juxtaarticular osteopenia
- Erosion
RA treatment
NSAIDS (celecoxib, diclofenac)
Glucocorticoids with FARME
FARME:
- Biologics = anti TNF (ethanercept), anti IL-6 (toxilizumab)
- Non-biologic = methotrexate
RA diagnostic criteria, at least 6 points in: (4)
Articular:
- 2-10 big = 1
- 1-3 small = 2
- 4-10 small = 3
- >10 at least 1 small = 5
Serology (FR, ACPA)
- Positive low = 2
- Positive high = 3
Sinovitis duration: >=6 weeks = 1
PRC, ESR abnormal = 1
