Lupus Flashcards

1
Q

definition of systemic lupus erythematosus

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

criteria for SLE

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

clinical criteria for SLE

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

immunologic criteria for SLE

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

malar rash

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Discoid lupus

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

alopecia in lupus

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

arthritis in lupus

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

serositis in lupus

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

nephritis in lupus

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

red cell casts

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

neurologic symptoms of lupus

A

seizures, psychosis, myelitis (cerebritis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

hematologic symptoms of lupus

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

lupus epidemiology

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

why are women more affected by lupus?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

genetics of lupus

A

cumulative effect of several genes is necessary, very heterogenous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

environmental factors for lupus

A

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

18
Q

autoantibodies

A

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

19
Q

pathway of self antigen presentation

A

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

20
Q

ANA

A

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

21
Q

how to measure ANAs?

A

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

22
Q

HEp2 cells

A

immortalized laryngeal epidermoid carcinoma cells

23
Q

anti dsDNA

A

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

24
Q

Anti Smith (SM)

A

specific for SLE, Speckled ANA fluorescent pattern

25
Q

anti-RNP

A

seen in both SLE and mixed connective tissue disease

26
Q

Anti-Ro/La (SSA/SSB)

A

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

27
Q

antiphospholipid antibodies

A

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

28
Q

possible pathogenic mechanisms for SLE

A

apoptosis, immune complex deposition, cytokine production, T cells

29
Q

abnormal apoptosis in SLE

A

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

30
Q

when do nuclear antigens present?

A

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

31
Q

apoptotic blebbing

A

main phagocytic targets

32
Q

neonatal lupus

A

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.

33
Q

immune complex deposition

A

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

34
Q

where do ICs deposit?

A

depends on size and charge

35
Q

complement levels in SLE

A

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

36
Q

cytokines important in lupus

A

Interferon and BLyS

37
Q

TLRs of SLE

A

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

38
Q

type 1 IFNs

A

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

39
Q

BLyS (BAFF)

A

B lymphocyte stimulator, promotes increase B cell survival.

40
Q

anti-BLyS antibody?

A

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

41
Q

how t cells cause damage in lupus

A

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