State of the Art on Nailfold Capillaroscopy
State of the Art on Nailfold Capillaroscopy
Two main categories of serum SSc biomarker have been investigated in correlation with the different nailfold videocapillaroscopic (NVC) patterns: angiogenic/static, vasculogenic factors and autoantibodies. Angiogenesis is heavily disturbed in SSc as mirrored by pathognomonic capillaroscopic changes (see above). In addition, despite the hypoxic conditions induced by the progressive SSc fibrosis and capillary number decrease, there is no evidence for sufficient compensatory angiogenesis in SSc.
One culprit may be an imbalance between angiogenic and angiostatic factors. Also vasculogenesis may be impaired. Cross-sectional associations have been described between microangiopathy (as assessed by capillaroscopy) and three angiogenic [vascular endothelial growth factor (VEGF), angiopoietin 2 (Ang-2) and endothelin-1 (ET-1)], one angiostatic factor (endostatin) and one vasculogenetic factor (Table 2).
The following associations between antibodies and capillaroscopy have been described in SSc: associations with anti-endothelial cell antibody (AECA) and with SSc-specific antibodies. AECA serum levels were recently found to be higher in patients with the late NVC pattern compared with the early and active ones (P = 0.04 and P < 0.02). In addition, higher skin scores and cardiovascular involvement were related to the presence of AECA and more severe microvascular changes, suggesting that AECA may have a role in the progression of endothelial damage and SSc disease.
Concerning SSc-specific antibodies, studies in populations with established and early SSc have been described. In established SSc, the prevalence of anti-Scl70 antibodies is significantly higher in the active and late vs the early patterns (P < 0.001), whereas the prevalence of ACA was highest in patients with the early NVC pattern.
In early SSc, prospective follow-up in those patients with RP who are prone to develop SSc has attested a sequence in the occurrence of microcirculatory changes, more specifically, first, appearance of giants, before the onset of clinically overt SSc and second, loss of capillaries, around the same time as occurrence of clinically overt disease. Also a varying time course for occurrence of microcirculatory damage after onset of RP depending on SSc antibody specificity has been described in this early SSc population.
In this way, giant capillaries occur earliest in patients with anti-RNAP III antibodies, latest in those with anti-CENP-B antibodies, whereas time of occurrence was intermediate with anti-Th/To (P = 0.002). A similar temporal development occurred for capillary loss in relationship to these three antibodies (P = 0.021). Further research, based on these associations, will clarify the role of the immune response in the pathogenesis and progression of SSc.
Links Between SSc Serum Biomarkers and Capillaroscopic Scleroderma Patterns
Two main categories of serum SSc biomarker have been investigated in correlation with the different nailfold videocapillaroscopic (NVC) patterns: angiogenic/static, vasculogenic factors and autoantibodies. Angiogenesis is heavily disturbed in SSc as mirrored by pathognomonic capillaroscopic changes (see above). In addition, despite the hypoxic conditions induced by the progressive SSc fibrosis and capillary number decrease, there is no evidence for sufficient compensatory angiogenesis in SSc.
One culprit may be an imbalance between angiogenic and angiostatic factors. Also vasculogenesis may be impaired. Cross-sectional associations have been described between microangiopathy (as assessed by capillaroscopy) and three angiogenic [vascular endothelial growth factor (VEGF), angiopoietin 2 (Ang-2) and endothelin-1 (ET-1)], one angiostatic factor (endostatin) and one vasculogenetic factor (Table 2).
The following associations between antibodies and capillaroscopy have been described in SSc: associations with anti-endothelial cell antibody (AECA) and with SSc-specific antibodies. AECA serum levels were recently found to be higher in patients with the late NVC pattern compared with the early and active ones (P = 0.04 and P < 0.02). In addition, higher skin scores and cardiovascular involvement were related to the presence of AECA and more severe microvascular changes, suggesting that AECA may have a role in the progression of endothelial damage and SSc disease.
Concerning SSc-specific antibodies, studies in populations with established and early SSc have been described. In established SSc, the prevalence of anti-Scl70 antibodies is significantly higher in the active and late vs the early patterns (P < 0.001), whereas the prevalence of ACA was highest in patients with the early NVC pattern.
In early SSc, prospective follow-up in those patients with RP who are prone to develop SSc has attested a sequence in the occurrence of microcirculatory changes, more specifically, first, appearance of giants, before the onset of clinically overt SSc and second, loss of capillaries, around the same time as occurrence of clinically overt disease. Also a varying time course for occurrence of microcirculatory damage after onset of RP depending on SSc antibody specificity has been described in this early SSc population.
In this way, giant capillaries occur earliest in patients with anti-RNAP III antibodies, latest in those with anti-CENP-B antibodies, whereas time of occurrence was intermediate with anti-Th/To (P = 0.002). A similar temporal development occurred for capillary loss in relationship to these three antibodies (P = 0.021). Further research, based on these associations, will clarify the role of the immune response in the pathogenesis and progression of SSc.
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