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© 1995 British Society for Rheumatology


research-article

SERIAL CIRCULATING ADHESION MOLECULE LEVELS REFLECT DISEASE SEVERITY IN SYSTEMIC SCLEROSIS

C. P. DENTON, M. C. M. BICKERSTAFF, X. SHIWEN, M. T. CARULLI, D. O. HASKARD*, R. M. DUBOIS{dagger} and C. M. BLACK

Rheumatology Research Unit, Royal Free Hospital London NW3 2QG
*Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital London W12 0NN
{dagger}Interstitial Lung Disease Unit, Royal Brompton Hospital London SW3 6LR

Correspondence to: Correspondence to: Carol M. Black, Rheumatology Research Unit, Royal Free Hospital, Pond Street, London NW3 2QG.

Microvascular damage occurs in systemic sclerosis (SSc) and is associated with increased expression of endothelial adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Elevated levels of the soluble circulating forms of these molecules have recently been reported in SSc. We have extended this observation by collecting serial serum samples from 12 patients with systemic sclerosis, at intervals between 4 and 12 months, through the course of their disease (mean period of observation 44 months). Circulating ICAM-1, VCAM-1 and E-selectin were measured by ELISA, and changes in these levels were compared with alterations in disease activity as assessed by skin sclerosis score, serum creatinine, erythrbcyte sedimentation rate and pulmonary function tests coincident with each serum sample. The mean levels were ICAM-1 627 ng/ml, VCAM-1 959 ng/ml and E-selectin 81 ng/ml. In 8/12 patients, there was a substantial change in at least one disease parameter during the assessment period. In seven (88%) of these patients, changes in circulating VCAM-1 or E-selectin were associated with disease severity, falling with improvement in renal function or skin score, and rising with deterioration in pulmonary function tests. The maximum recorded level of VCAM-1 (3550 ng/ml) shortly preceded an acute renal SSc crisis. In two cases (25%), the correlation was statistically significant (P ≤ 0.01). The ICAM-1 level did not reflect clinical changes in any patients. These results provide further evidence for endothelial cell dysfunction in SSc, and suggest that serial measurements of VCAM-1 and E-selectin may have potential value as surrogate markers for clinical progression or remission in this disease.

KEY WORDS: Scleroderma, Lung fibrosis, Nephropathy, Adhesion molecules


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