Lupus

Question 1

definition of systemic lupus erythematosus

Answer 1

a systemic autoimmune disease characterized by the production of antibodies to the components of a cell nucleus in association with protean clinical manifestations

Question 2

criteria for SLE

Answer 2

> 4 criteria fulfilled. Must have at least one clinical and one lab OR biopsy proven lupus nephritis with positive ANA or anti-DNA

Question 3

clinical criteria for SLE

Answer 3

malar rash, discoid rash, oral/nasal ulcers, non-scarring alopecia, arthritis, serositis, renal, neurologic, hemolytic anemia, thrombocytopenia, leucopenia

Question 4

immunologic criteria for SLE

Answer 4

ANA (anti nuclear antibody), anti-dsDNA, Anti-Smith, anti phospholipid antibodies, low complement levels (C3,4), positive direct coombs test

Question 5

malar rash

Answer 5

acute cutaneous lupus, butterfly rash die to photosensitivity. Cheeks and nose. Non-scarring.

Question 6

Discoid lupus

Answer 6

chronic cutaneous lupus, red raised disc shaped patches. can be anywhere on body. scarring.

Question 7

alopecia in lupus

Answer 7

diffuse thinning or hair fragility with visible broken hairs, in the absence of other causes

Question 8

arthritis in lupus

Answer 8

tends to be non-erosive (jacoud’s: erosion of MC heads and ulnar deviation)

Question 9

serositis in lupus

Answer 9

inflammation around the lining of the lung or heart that causes chest pain when taking a deep breath. Lung=pleuritis, heart=pericarditis

Question 10

nephritis in lupus

Answer 10

protein in urine (>500mg/24hrs) &/or red cell casts

Question 11

red cell casts

Answer 11

red cells from the glomerulus of the kidney surrounded by a proteinacious matrix, indicative of inflammation and damage to the kidney

Question 12

neurologic symptoms of lupus

Answer 12

seizures, psychosis, myelitis (cerebritis)

Question 13

hematologic symptoms of lupus

Answer 13

hemolytic anemia (coombs positive), leukopenia or lymphopenia, thrombocytopenia

Question 14

lupus epidemiology

Answer 14

females:male=15:1, can present at any age. children/men tend to be more severe, uncommon in europeans/africans,

Question 15

why are women more affected by lupus?

Answer 15

X chromosome may contribute? pregnant lupus patients have less of an estrogen/progesterone surge during late trimesters, UNKNOWN

Question 16

genetics of lupus

Answer 16

cumulative effect of several genes is necessary, very heterogenous

Question 17

environmental factors for lupus

Answer 17

viruses like EBV (molecular mimicry?), UV light (increased cytokines?), smoking

Question 18

autoantibodies

Answer 18

antibodies that recognize self antigens generated during antibody assembly and pass through defective check point system. LOSS OF SELF TOLERANCE

Question 19

pathway of self antigen presentation

Answer 19

APCs are hyper activated by environmental, viral or other trigger, so they phagocytose self antigen and are activated. They then present self-antigen to host lymphocytes which should have been killed during development

Question 20

ANA

Answer 20

anti-nuclear antibodies that bind to antigens found in the nucleus of the cell.

Question 21

how to measure ANAs?

Answer 21

indirect immunofluorescence & ELISA. HEp2 cells are coated with patient serum and Ab:Ag complexes are detected via anti-human fluorescence labeled antibodies. Serial dilutions tested to determine titer volume of antibodies

Question 22

HEp2 cells

Answer 22

immortalized laryngeal epidermoid carcinoma cells

Question 23

anti dsDNA

Answer 23

specific for SLE and titer fluctuates with disease activity. associated with active glomerulonephritis, perinuclear ANA fluorescent pattern

Question 24

Anti Smith (SM)

Answer 24

specific for SLE, Speckled ANA fluorescent pattern

Question 25

anti-RNP

Answer 25

seen in both SLE and mixed connective tissue disease

Question 26

Anti-Ro/La (SSA/SSB)

Answer 26

seen in SLE and with Sjogrens Syndrome and pathogenic in neonatal lupus.

Question 27

antiphospholipid antibodies

Answer 27

antibody to phospholipid part of cell membrane thought to make blood more susceptible to clotting, causing clots in arteries, veins, and increased risk of miscarriage

Question 28

possible pathogenic mechanisms for SLE

Answer 28

apoptosis, immune complex deposition, cytokine production, T cells

Question 29

abnormal apoptosis in SLE

Answer 29

self antigens are normally recognized when cells apoptose, but in SLE phagocytosis and IC clearing is defective due to deficient Fc and complement receptors

Question 30

when do nuclear antigens present?

Answer 30

appear within apoptotic blebs or are released during blebbing. impaired phagocytosis leads to persistence of antigen and immune complexes

Question 31

apoptotic blebbing

Answer 31

main phagocytic targets

Question 32

neonatal lupus

Answer 32

mother's anti-Ro/La crosses the placenta and gets into the fetal circulation and binds fetal myocardiocyte after blebs containing Ro antibody are exposed, causing inflammation and cell death. manifests as conduction abnormality and causes death in utero.

Question 33

immune complex deposition

Answer 33

IC activates complement system, which causes recruitment of inflammatory cells, IC gets phagocytosed and additional mediators of inflammation are released.

Question 34

where do ICs deposit?

Answer 34

depends on size and charge

Question 35

complement levels in SLE

Answer 35

the lower the complement (C3/4), the higher the disease activity because consumption indicates IC clearing

Question 36

cytokines important in lupus

Answer 36

Interferon and BLyS

Question 37

TLRs of SLE

Answer 37

7/9. activated by ICs to stimulate dendritic cells, which then release type 1 interferons

Question 38

type 1 IFNs

Answer 38

first responder to infection, potent promoter of inflammatory response and promotes survival of auto reactive B cells. higher level=increased disease activity

Question 39

BLyS (BAFF)

Answer 39

B lymphocyte stimulator, promotes increase B cell survival.

Question 40

anti-BLyS antibody?

Answer 40

Belimumab (Benlysta). targeted monoclonal antibody that binds to soluble BLyS, allowing more B cells to undergo apoptosis, preventing survival of auto reactive B cells

Question 41

how t cells cause damage in lupus

Answer 41

stimulate autoreactive b cells via cytokines, can also directly damage tissues (CTL)