Systemic Lupus Erythematosus: What lies beneath
TNF -‐ ALPHA
TNF -‐ ALPHA That’s All I Knew!!
YOU CAN UNDERSTAND IT! JUST OPEN YOUR MIND!
Impaired immune system in SLE
Guerra et al. Arthri+s Research & Therapy 2012 14:211
The pathogenesis of Systemic Lupus Erythematosus (SLE) involves: • B cells • T Cells • Complement • All of the above
SLE Pathogenesis: The Panoramic View
Reumatologica Clinica 2012
DefecKve clearance in this process leads to increased release of auto-‐anKgens: • Tolerance • Cellular ProliferaKon • Apoptosis • TransformaKon
Apoptosis: Programmed Cell Death
Some;mes things don’t go as Programmed…..
Complement in the pathogenesis of SLE
Sturfelt, G. & Truedsson, L. (2012) Complement in the immunopathogenesis of rheumaKc disease Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2012.75
The complement pathway most involved in SLE is: • AlternaKve Pathway • Classical Pathway • Neoclassical Pathway • Straight Pathway
CYTOKINES IN SLE
Cytokines in SLE
• decreased expression of interleukin (IL)-‐2 • increased produc;on of IL-‐17 and related cytokines
• B-‐cell ac;va;ng factor, which promotes B-‐cell survival and autoan;body produc;on
• interferon-‐α, which acts as an immune adjuvant
• tumor necrosis factor, which contributes to organ inflamma;on
Nature Reviews Rheumatology 6, 317-‐325 (June 2010)
Figure 1 Soluble BAFF and APRIL signalling
Vincent, F. B. et al. (2014) The BAFF/APRIL system in SLE pathogenesis Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2014.33
Figure 3 Role of BAFF in the pathogenesis of SLE
Vincent, F. B. et al. (2014) The BAFF/APRIL system in SLE pathogenesis Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2014.33
BAFF is a member of which cytokine superfamily? • Interferons • IL-‐10 • TNF-‐Alpha • Chemokines
Toll – Like Receptors : Lead to IFN-‐Alpha producKon in SLE
Liu et al Nature Medicine 2012
Interferon in SLE
IFN-‐α produced promotes a. DC1 development b. T cell acKvaKon c. autoanKbody producKon by B cells
The Toll Like Receptors primarily involved in SLE Pathogenesis are : • 23, 6, 24 • 10, 11, 12 • 7, 8, 9 • 21, 17, 10
End Organ Damage in SLE: What Gives?
Nature , 2012
Pathophysiology understanding drives treatment advances!
Dema, DiscoveryMedicine, May 2014
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