Circulating soluble adhesion molecules in ANCA-associated vasculitis.
BACKGROUND
To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF).


METHODS
A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis.


RESULTS
At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration.


CONCLUSIONS
Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.
Ara
J
J
Nephrology Service, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Mirapeix
E
E
Arrizabalaga
P
P
Rodriguez
R
R
Ascaso
C
C
Abellana
R
R
Font
J
J
Darnell
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000097:blood*; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D008875:Middle Aged; D019087:Selectins / Q000097:blood; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014657:Vasculitis / Q000097:blood* / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D015815:Cell Adhesion Molecules; D019087:Selectins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1