Systemic Lupus Erythematosus

Question 1

Overexpression of which TLR increase downstream interferon responses appear to drive SLE disease process

Answer 1

TLR7

Question 2

Which infection results in a defective T-cell response in SLE?

Answer 2

EBV infection

Question 3

How does EBV infection induce an autoimmune response?

Answer 3

Antibodies specific for the viral Epstein-Barr nuclear antigen 1 (EBNA1) protein can cross-react with dsDNA

Question 4

What effect does hydralazine have on DNA methylation?

Answer 4

Hydralazine inhibits extracellular signal-regulated kinase pathway signalling, which results in decreased expression of DNA methyltransferase (DNMT1) and DNMT3A, enzymes that mediate DNA methylation

Question 5

What’s the function of C1q protein in apoptosis?

Answer 5

Defective complement pathway may also contribute to ineffective clearance of apoptotic cells as C1q binds to cell debris, allowing macrophages with C1q receptors to engulf the apoptotic cells

Question 6

What cell provides the main source of type 1 IFNs?

Answer 6

Plasmacytoid dendritic cells

Question 7

Upon binding to TLR7 and TLR9 which type of IFN is produced?

Answer 7

Type 1 IFN

Question 8

What is the co-stimulatory molecule that T cells use to activate B cells

Answer 8

CD40

Question 9

Is there an increase of decrease in the numbers of Tregs in SLE?

Answer 9

Reduction

Question 10

Is there an increase or decrease in numbers of TH17 cells in SLE?

Answer 10

Increase

Question 11

Is there an increase or decrease in numbers of IL-17 in SLE?

Answer 11

Increase

Question 12

Is there an increase or decrease in IL-2 production in SLE patients

Answer 12

decrease

Question 13

Name the 4 autoantibodies targets in SLE?

Answer 13

1. DNA and DNA-binding proteins which are aggregated with histones in nucleosomes
2. RNA and RNA-associated proteins which are aggregated in cytoplasmic or nuclear ribonucleoprotein particles
3. B2-glycoprotein 1 in association with phospholipids
4. Cell membrane proteins typically those expressed on blood cells

Question 14

Which antibodies appear first in SLE?

Answer 14

Antinuclear antibodies, antibodies to Ro and antibodies to B2-glycoprotein 1

Question 15

Which antibodies appear 1-2 years before symptom onset?

Answer 15

Anti-dsDNA

Question 16

Which antibodies appear in the months immediately preceding symptoms?

Answer 16

Antibodies to Sm and RNP (ribonucleoprotein)

Question 17

What is immunoglobulin class switching driven by in autoantibodies in SLE

Answer 17

CD4+ T helper cells or TLR ligands or B-cell activating factor (BAFF)

Question 18

Name some pharmacological active non renal SLE treatment

Answer 18

Tacrolimus (macrolide with immunosuppressive properties)
Severe SLE - systemic glucocorticoids (as initiation therapy + maintenance immunosuppressive therapy in long term to allow tapering of glucocorticoid dose)

Question 19

Name the maintenance treatment of non-renal SLE?

Answer 19

1. Hydroxychloroquine (used for immunosuppressive actions and ability to reduce disease flares)
2. Azathioprine (purine analogue that blocks immune cell proliferation)
3. Mycophenolate mofetil (inhibitor of purine synthesis that blocks immune cell proliferation)

Question 20

Name some refractory nonrenal SLE treatments?

Answer 20

Belimumab (humanized recombinant IgG monoclonal antibody directed against B cell activating factor (BAFF)

Question 21

What’s the treatment of active lupus nephritis?

Answer 21

Initiation therapy is low dose glucocorticoids (prednisone)
Additional initiation therapy with mycophenolate mofetil is an established option with intravenous cyclophosphamide or rituximab as alternatives

ACE inhibitors or ARBs are often used as renoprotective agents