SSc Flashcards
Prevalence, onset and w/m ratio in SSc?
40-200/1Mio
40-50 years
3:1-5:1 (w/m)
Clinical symptoms of SSc
Raynaud, skin fibrosis, GIT complications, ulcers, interstitial lung disease, PAH, musculosceletal problems, telangiectasia
Name features of lcSSc
Skin lesions at distal acra, face, centripetal
Raynaud years before skin lesions
Slow and continous progression, sometimes constant
GIT and lung involvement (often years after)
ACA often pos.
Name features of dcSSc
Lesions: entire skin, centrifugal Raynaud: timely onset with lesions Relapsing and rapidly progressing course Organs: Joints, GIT, heart, lung, kidney ANti-Scl70 often pos.
With items does the ACR/EULAR classification include for SSc?
skin thickening, Raynaud, digital ulcers, PAH, SSc-related Ab
>9 = SSc
Name some important players in the pathogenesis of SSc
Damage/trigger at endothelial cells -> B cells (CD19 high, CD22 down) -> Plams cells -> Auto-Ab
Auto-Ab-> Endothelial cells (adhesion molecules incerased), cell activation, ROS, vasoconstriction, cell death -> endothelial dysfunction -> B&T cells (incerased Th2/Th17 response -> TGFb, IL6, IL4, IL13 -> Myofibroblasts
Auto-Ab -> fibroblasts -> myofibroblast -> ECM (intimal proliferation, proliferation of a-SMC -> vasculopathy and fibrosis)
Against which auto-ag are most auto-ab in SSc directed?
Topoisomerase 1 (Scl-70), anti-centromere, antinuclear ab (ANA)
dsSSc: Scl-70, RNAP3, fibrillerin
lcSSc: centromere, Th/To-ribonucleoprotein
Other: anti-ICAM1, ANti-AT1R/ETaR, MSRA
Pathogenecity of auto-ab in SSc
Antibody-dependent-mediated cell death (induction of cell death by Fc binding of cytotoxic cells)
Name features of auto-ab against GPCR in SSc
7TM receptors, in (non-)immune cells, involved in a variety of processes (cell transport, migration, neurotransmission)
AT1R and ETaR
receptor expression is higher in patients with lung fibrosis (in SSc)
Anti-AT1R ab induce cellular events associated with disease pathogenesis (Collagen expression -> fibrosis; neutrophil recruitment)
Binding of Auto-ab to GPCR leads to:
Production of TGFb, CCL18, collagen, incerase of VCA;1, incerase of sensibility of receptor to ang2 and endothelin1
Induction of chemotaxis, cell migration and fibrosis
Whats the role of cytokines in SSc?
Impaired communication between tissues and the immune systeme -> cause and consequence: abnormalities in the action of cytokines
Th1/2/17 cytokines (Il10, IL17, TNFa, TGFb, IFNg..) lead to inflammation, fibrosis, endothelial activation (ICAM, VCAM, Selectins), ECM mechanical stress
Whats the role of CCL18 and IL8 in SSc?
Alternative activation of macrophages (release induced by Auto-ab)
Whta the role of EV in SSc?
EV may be chemoattractants or ative producer of chemoattractants, EV and Auto-ab dustrub ECM homeostasis
Therapy for __ and __ in SSc
Vasculopathy (Raynaud, acral ulcers, PAH) and inflammatory fibrosis (cutaneous/musculoskeletal manifestations, interstitial lung disease, cardiac manifestation)
And GIT, calcinosis cutis
Important drugs for the therapy of SSc
MTX, Ciclosporin A (IL2, calcineurin down), Azathioprine (purine analogue), Mycophenolic acid, Tocilizumab (IL6-R blocker), Cyclophosphamide (DNA synthesis disrupted), Rituximab /a-CD20 ab), Nitedanibe (blocks VEGF, EGF, PDGF)
