RA/SLE

Question 1

What is the sex bias with RA and SLE?

Answer 1

mostly women are affected, RA especially develops during younger years

Question 2

What are some common symptoms of RA?

Answer 2

joint pain and stiffness in the morning with persistent swelling (bilateral and symmetrical – not on a weight bearing joint)

Question 3

What is epitope spreading?

Answer 3

IS sees one thing initially, then it sees more epitopes

Question 4

Why does smoking tend to trigger RA?

Answer 4

smoke citrullinates peptides via PAD2/4, so the IS sees a new Ag and produces ACPAs (anti citriullinated protein Abs)

Question 5

what is a tertiary lymphoid structure?

Answer 5

congregation of ICs where they shouldn’t be – produce germinal centres

Question 6

Where in the joint during RA is the teritiary lymphoid structure/inflammatory pannus? What are some characterisitics of IC infiltration of the joint?

Answer 6

in the marginal area – in the synovium

enhanced blood flow
enhanced angiogenesis

Question 7

Describe how inflammation causes RA

Answer 7

Ab + C1q = immune complexes

Ab + C1q –> macrophages –> activates osteoclasts + RANKL

RANKL –> activates osteoclasts

Question 8

What causes mortality in younger patients with RA?

Answer 8

CVD

Question 9

What are common symptoms of SLE?

Answer 9

• previous clots
• ongoing joint stiffness and pain in the morning with intermittent swelling and chest pain (similar to RA expect with the addition of chest pain)
• photosensitive rash/hives –> especially the butterfly rash on face

Question 10

As lupus gets more aggressive, where do you see more complement deposition?

Answer 10

kidneys – glomerulus

Question 11

What Ab isotypes can mediate the classical complement cascade?

Answer 11

IgM and IgG

Question 12

Describe the complement pathway for all three cascades

Answer 12

classical: Ag-Ab complex + C1, C4, C2 –> C3 convertase (C3 –> C3b) –> C5 convertase (C5 –> C5b) –> C5b, C6, C7, C8, C9 –> MAC

alternative: activating surfaces (e.g. LPS) –> C3b + factor B + factor D –> C3 convertase –> etc

lectin: C4, C2, MBL –> C3 convertase –> etc

Question 13

What triggers the lectin pathway and the alternative pathway, respectively?

Answer 13

lectin = bacterial slime basically
alternative = inflammation

Question 14

Besides Abs and lectins, what can trigger complement?

Answer 14

NETs from neutrophils

Question 15

Describe the pathogenesis of SLE

Answer 15

1. infection, UV light and drugs can trigger apoptosis
2. apoptotic material, rich in lupus autoAg, promotes the activation of DCs and B cells and the production of IFN and autoAbs, respectively
3. autoAgs are pesented by DCs –> T cell activation
4. activated T cells help B cells to produce Abs by the secretion of IFNg, IL-17, and by cell surface molecules (e.g. CD40L and CTLS4)
5. production of autoAbs is driven by the availability of endogenous Ags and is highly dependent up T cell help, mediated by cell surface interactions (CD40/CD40L) and cyotkines (IL-21)
6. T cell independent mechanisms of B cell stimulation may occur via combined BCR and TCR signaling
7. in lupus nephritis, pCDs infiltrate the kidney

Question 16

What kind of mortality is SLE associated with?

Answer 16

all cause mortality

Question 17

Describe two ways in which complement activation can cause thrombosis or hemolysis

Answer 17

1. PNH: cells lack the complement inhibitors CD55 and CD59 –> chronic surface activation of complement –> hemolysis and thrombosis
2. APS/CAPS: aPl-Abs bind to platlets surfaces –> activate complement –> thrombosis

Question 18

why are clots common in SLE pts?

Answer 18

damage to endothelium from autoAbs –> complement activation + NETosis –> thrombosis

Question 19

what are four autoimmune cytopenia manifestations of SLE?

Answer 19

1. hemolytic anemia
2. neutropenia
3. lymphopenia (Tregs are depleted)
4. thrombocytopenia (less platlets)

Question 20

Why are cytopenias bad?

Answer 20

• infection: more restrictured TCR repertoire, more opportunistic infections, fewer PMNs
• more bleeding
• more clotting
• epitope spreading and more survival advantages of self-reactive T cells (less diverse T and B cell populations –> expansion of reactive lymphocytes)