Autoimmunity

Question 1

SLE common mutations

Answer 1

HLA-DR2 or DR3

Question 2

Effect of estradiol on SLE

Answer 2

Less apoptosis of autoreactive B cells
Increase: IL-1, VCAM

Question 3

SLE pathogenesis

Answer 3

UV/damage —> stress, ROS —> apoptosis —> inadequate clearance = NUCLEAR ANTIGENS

Defective self-tolerance —> ANAs —> immunocomplexes —> inflammation

Question 4

SLE hypersensitivity

Answer 4

Type III

Question 5

Endosomal TLR effect in SLE

Answer 5

B cells produce more ANAs —> DCs —> IFNa —> more response

Question 6

Antibody types in SLE (4)

Answer 6

• ANAs
• Anti-smith vs ribonucleoproteins
• Anti-dsDNA (active disease)
• Anti-phospholipid

Question 7

Anti-phospholipid antibodies types (3) and effect

Answer 7

• Anti-cardiolipin (also in syphilis)
• Lupus anticoagulant vs prothrombin
• Anti-b2 glycoprotein 1

HYPERCOAGULATIVE

Question 8

DIAGNOSTIC antibodies in SLE

Answer 8

Smith and dsDNA

Question 9

ANAs are hypersensitivity type III, what about the other antibodies in SLE?

Answer 9

Type II

Question 10

Diagnostic criteria for SLE (11)

Answer 10

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

Question 11

Complex responsible for thrombus in SLE

Answer 11

Phospholipid b2 glycoprotein I complex

Question 12

Virchow’s triad

Answer 12

• Venous stasis
• Endothelial damage
• Procoagulative state

Question 13

SLE lab findings (not typically done)

Answer 13

• Low C3 and C4
• High ESR, CRP
• CBC all low
• High BUN, creatinine
• Electrolyte abnormalities
• RPR and VDRL positive

Question 14

Nephritis in SLE

Answer 14

Diffuse proliferative glomerulonephritis

Question 15

SLE treatment

Answer 15

• Glucocorticoids —> Cushings
• Immunosuppressants when severe
• Hydroxychloroquine

Question 16

RA gene mutation

Answer 16

HLA - DRB1

Question 17

RA pathogenesis

Answer 17

Damage —> citrulination or carbamylation = neoantigens

—> immune complexes —> deposit in synovial membrane —> activate osteoclasts = erosive

Question 18

RA triggers (3)

Answer 18

Cigarette
HLA-DRB1
Infections: P.gingivalis, Prevotella (GI)

Question 19

Autoantibodies in RA

Answer 19

ACPA
RF - target IgG

Question 20

Fibroblast-like synoviocytes function in RA

Answer 20

Make MMP13 —> adheres to and invades cartilage

Question 21

RA stages

Answer 21

Preclinical: ACPA, RF, cytokines

10 years

Early RA: CD4+, MQ, stromal cell activation, MMP line cavity
Established RA: MQ and fibroblasts

Question 22

Synovium in RA

Answer 22

Synoviocytes and FLS expand —> IL-1, IL-6, TNF, MMP, PG, leukotrienes, microRNA

Fill with fibroblasts, adipocytes, vessels, immune cells

Question 23

Joint damage in RA

Answer 23

MQ, neutrophils, mast cells —> cytokines and MMPs
MMPs: collagenases, stromelysins destroy cartilage

Question 24

RA clinical manifestations (7)

Answer 24

• Peripheral and small proximal joints
• C1&C2
• Morning rigidity
• Symmetric, polyarticular
• Erosive
• 4 ORs: calor, tumor,
• Vasculitis

Question 25

Deviations in RA

Answer 25

Cubital in wrist Boutonniere/Ojal: fold, extend Swan: extend, fold Z thumb

Question 26

Rx in RA (3)

Answer 26

- Less articular space - Juxtaarticular osteopenia - Erosion

Question 27

RA treatment

Answer 27

NSAIDS (celecoxib, diclofenac) Glucocorticoids with FARME FARME: - Biologics = anti TNF (ethanercept), anti IL-6 (toxilizumab) - Non-biologic = methotrexate

Question 28

RA diagnostic criteria, at least 6 points in: (4)

Answer 28

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