Pathoma - Autoimmune disorders

Question 1

What is the role of the AIRE gene

Answer 1

It allow medullary epithelial cells of the thymus to display self-antigens during negative selection

Mutation will prevent developing lymphocytes from being tested against self-antigens, and allowed to be released, leading to autoimmunity

Question 2

What are the 2 methods of peripheral tolerance of lymphocytes?

Answer 2

(1) Anergy: T-cells bind to MHC/antigen complex, and if there is no second activation signal (CD28 binding B7) the cell will shut down
(2) Apoptosis: if the T-cell keeps binding the MHC/antigen without a 2nd signal, the T-cell will begin to express FasL which will bind to death receptors

Question 3

What cytokines to regulatory T-cells produce?

Answer 3

IL-10 and TGF-B

Question 4

What molecules to Treg cells express/are positive for?

Answer 4

CD4+
CD25+
FOXP3+

Question 5

What is Autoimmune lymphoproliferative syndrome (ALPS) caused by?

Answer 5

Mutation in the Fas apoptosis pathway, allowing self-reactive lymphocytes to continue proliferating and produce antibodies against normal cells

Question 6

Describe bystander activation in the setting of autoimmunity

Answer 6

Patient makes a few self-reactive lymphocytes, but then gets an infection which ramps up the immune system causing self-reactive lymphs to multiply

Question 7

Describe molecular mimicry in the setting of autoimmunity

Answer 7

Patient is infected with something similar to self-antigen, so self-reactive lymphocytes are increased because they are similar

Question 8

What type of hypersensitivity reaction is SLE?

Answer 8

Type III

Question 9

Describe the mechanism behind the development of SLE

Answer 9

Poorly cleared apoptotic debris (e.g. from UV damage) activates self-reactive lymphocytes, which then produce antibodies to host nuclear antigens

Question 10

How is complement deficiency a cause of SLE

Answer 10

If complement cannot clear the apoptotic debris, it will remain around for cells to make antibodies against them

Question 11

What are the 11 criteria of SLE:

Answer 11

RASH OR PAIN

Rash (malar or discoid)
Arthritis
Serositis
Hematologic disorders (e.g. anemia, thrombocytopenia, leukopenia)
Oral/nasopharyngeal ulcers
Renal disease
Photosensitivity
Antinuclear antibodies (ANA)
Immunologic disorder (anti-dsDNA, anti-Sm, anti-phospholipid)
Neurologic disorders (psychosis or seizures)

Question 12

What are the 2 types of renal damage associated with SLE?

Answer 12

Nephrotic: membranous nephropathy

Nephritis: diffuse proliferative glomerulonephritis

Question 13

What type of hypersensitivity reaction is there against blood cells in lupus

Answer 13

Type II (antibody directly against cells)

Question 14

What is Libman-Sacks endocarditis (associated with SLE)

Answer 14

Small vegetations on BOTH SIDES (top and bottom) of mitral valve

Question 15

What are anti-Smith antibodies directed against?

Answer 15

snRNPs

Question 16

What complements will be decreased in SLE?

Answer 16

CH50, C4, and C3

Question 17

What type of antibody is anticardiolipin and what can it cause false positives in?

Answer 17

It is an antiphospholipid in SLE

Can cause false-positive for syphilis

Question 18

What type of antibody is lupus anticoagulant and what can it falsely elevate?

Answer 18

It is an anti-phospholipid

Can falsely elevate PTT

Question 19

What are the diagnostic criteria of antiphospholipid antibody syndrome (APA)

Answer 19

Hypercoagulable state with + antiphospholipids( e.g. lupus anticoagulant, anticardiolipin, anti-B2-glycoprotein)

Question 20

What is paradoxical about antiphospholipid antibody syndrome

Answer 20

Lupus anticoagulant can lead to increased PTT, but the syndrome actually causes HYPERcoagulability

Question 21

What is the characteristic antibody in drug-induced lupus

Answer 21

Antihistone antibody

ANA is also positive by definition

Question 22

What drugs are common causes of drug-induced lupus

Answer 22

SHIPP-E:
♣	S – sulfa drugs
♣	H – Hydralazine
♣	I – Isoniazid
♣	P – Procainamide
♣	P – Phenytoin
♣	E – Etanercept

Question 23

What clinical findings are usually absent in Drug-induced lupus that are present in SLE

Answer 23

Renal and CNS involvment

Question 24

Most common cause of death in SLE?

Answer 24

Renal failure, infection, and accelerated coronary atherosclerosis

Question 25

What type of hypersensitivity is Sjogren syndrome?

Answer 25

Type IV (lymphocyte-mediated)

Question 26

What are the 3 major diagnostic criteria in Sjogrens?

Answer 26

(1) Dry eyes/mouth
(2) ANA + anti-SSA/anti-SSB/anti-RF
(3) Lymphocytic sialadenitis

Question 27

What type of antibodies are anti-SSA and anti-SSB

Answer 27

anti-ribonucleoprotein antibodies

Question 28

What is the risk for pregnant women with anti-SSA?

Answer 28

Neonatal lupus and congenital heart block

Question 29

What disease does Sjogren’s increase the risk of?

Answer 29

B-cell (marginal zone) lymphoma

Will present as unilateral enlargement of parotid gland late in the disease course of Sjogren’s

Question 30

What is the cause of Systemic Sclerosis (Scleroderma)

Answer 30

Fibroblast activation leading to deposition of collagen

Autoimmune disorder characterized by sclerosis of skin and visceral organs

Question 31

Describe the disease process leading to fibroblast activation in Scleroderma

Answer 31

Autoimmune damage to endothelial cells

Damaged endothelium causes vasoconstriction (increased endothelin and decreased NO) and secretion of growth factors (TGF-B and PDGF), which activate fibroblasts

Question 32

What are the antibodies in limited-type and diffuse-type Scleroderma?

Answer 32

Limited-type: anti-centromere

Diffuse-type: anti-DNA topoisomerase

Question 33

What are the characteristics of limited-type scleroderma and describe the protype

Answer 33

Limited skin involvement (hands and face) with late visceral involvement

CREST syndrome:
C - Calcinosis (deposition of calcium in subcutaneous tissue / anti-Centromere
R - Raynoud
E - Esophogeal dysmotility
S - Sclerodactyly (fibrosis of skin of hands/tightening of skin/loss of wrinkles)
T - Telangiectasias

Question 34

What are the characteristics of diffuse-type scleroderma

Answer 34

Diffuse skin involvement with early visceral involvement

Question 35

What are the 3 diseases that have mixed features in Mixed Connective Tissue disease

Answer 35

SLE, systemic sclerosis, polymyositis

Question 36

What antibody is associated with mixed connective tissue disease

Answer 36

anti-U1 ribonucleoprotein