Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
The Interplay of Vascular Function, Low Grade Inflammation and Innate Immunity in Raynauds Phenomenon and Systemic Sclerosis
Anderson, Marina E., Barnes, Theresa, Pyrkotsch, Paula, Lamb, Janette, Naylor, Emma, Edwards, Steven W., Moots, Robert J.
The pathophysiological processes underlying systemic sclerosis (SSc) are incompletely understood, despite considerable morbidity and risk of early mortality in this multi-system disease. However, preliminary work from our department suggests that, in addition to well-described vascular, fibrotic and immunological abnormalities, low-grade inflammation and innate immunity play a role. Our aim was to investigate the link between inflammation, innate immunity and vasculopathy in this disease.
In our cohort of patients with limited and diffuse cutaneous SSc (lcSSc and dcSSc), primary RP (PRP), undifferentiated connective tissue disease (UCTD) and healthy control subjects, we studied three groups of parameters:1)
NK cells and neutrophils: peripheral blood2)
Markers of inflammation and vascular activation: peripheral blood3)
Macrovascular function: Applanation tonometryb)
Microvascular morphology: Digital nailfold video capillaroscopyc)
Microvascular function: Digital iontophoresis of acetylcholine (ACh, endothelial-dependent vasodilatation) and nitroprusside (NP, endothelial-independent vasodilatation) measured by laser Doppler imaging.
Spearman's rank correlation coefficient was used to examine the relationship between the three groups of parameters.
Having determined, in 40 subjects (9 controls, 5 PRP, 4 UCTD & 22 SSc), that there are significant differences between the studied subject groups of1)
markers of apoptosis (annexin V), activation (CD16) & adhesion (CD11b & CD18) on isolated neutrophils2)
markers of endothelial activation (VCAM-1, E-selectin & ET-1) and inflammation (IL-6) in sera, and3)
tests of vascular function/morphology,
we correlated our findings to examine the relationship between variables.
Significant correlations between markers of neutrophil/endothelial activation and vascular morphology/function are shown in table 1.
Table 1. Correlations between markers of neutrophil/endothelial activation and vascular morphology/function
|Spearman's rho correlation coefficient (p)|
|lcSSc||Annexin V vs ACh iont||-0.929 (<0.001)|
|Annexin V vs NP iont||-0.857 (0.007)|
|CD11b vs Loops/mm||0.700 (0.036)|
|All disease groups||Annexin V vs ACh iont||-0.591 (0.016)|
|Annexin V vs NP iont||-0.544 (0.029)|
|E-selectin vs Loops/mm||-0.419 (0.024)|
|ET-1 vs Appl tonometry||0.620 (0.018)|
|IL-6 vs ACh iont||-0.388 (0.034)|
|IL-6 vs Loops/mm||-0.414 (0.026)|
Significant correlations were also seen between IL-6, ET-1 and cellular adhesion molecules in the disease states.
We demonstrated that 1)neutrophil apoptosis and 2)markers of both neutrophil and endothelial adhesion/activation are associated with micro- and macro-vascular function and morphology in RP and SSc, suggesting that low-grade inflammation, innate immunity and the micro-/macro-circulation play an integrated role in the pathogenesis of SSc.
Further work is underway to further characterise the role of both the innate immune system and the vasculature, and the interplay of these two systems in SSc, with the ultimate aim of identifying new markers of disease activity and severity.
To cite this abstract, please use the following information:
Anderson, Marina E., Barnes, Theresa, Pyrkotsch, Paula, Lamb, Janette, Naylor, Emma, Edwards, Steven W., et al; The Interplay of Vascular Function, Low Grade Inflammation and Innate Immunity in Raynauds Phenomenon and Systemic Sclerosis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1817