Antiendothelial Cell Antibodies: Useful Markers of Systemic Sclerosis

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Abstract

BACKGROUND: Systemic sclerosis (SS) encompasses a wide spectrum of clinical presentations. Antiendothelial cell antibodies (AECA) in patients with primary Raynaud's phenomenon (PRP), limited SS (lSSc), or diffuse SS (dSSc) may help to determine the long-term prognosis of the disease.

METHODS: Twenty-seven normal controls, 13 patients with PRP, 36 with lSSc, and 31 with dSSc were included in the study. Sera were examined for the presence of AECA, using a cellular enzyme-linked immunosorbent assay (ELISA). Angiotensin-converting enzyme (ACE) activity, plasma von Willebrand factor antigen (vWfAg), and thrombomodulin (Tm) concentrations were also evaluated. The medical records of 50 of the lSSc and dSSc patients were reviewed and the organ system involvement noted.

RESULTS: Antiendothelial cell antibodies were present in 3 patients with PRP, 16 patients with lSSc, and 26 patients with dSSc. These autoantibodies were mainly of the IgG isotype. There was no difference in ACE activity between patients and controls. In contrast, vWfAg and Tm concentrations were higher in patients with PRP relative to controls, and higher in patients with lSSc compared with those with PRP. The presence of AECA was associated with digital scars and ulcers (P < 0.004 and P < 0.003, respectively), severe RP (P < 0.01), grade 3 tortuosity of vessels (P < 0.0004), and lung involvement (P < 0.02).

CONCLUSION: The significant trend for AECA to increase with disease severity across the three groups of patients studied suggests that the AECA test can identify subsets of SSc with differing prognoses.

Section snippets

Source of Sera

Sixty-seven Caucasian patients with SSc were recruited by faculty members in the Institute of Rheumatology at the University of Moscow, Russia, all fulfilling the American College of Rheumatology preliminary criteria for definite SSc.[18] Patients with skin thickening confined to face and extremities were classified as having lSSc (n = 36; 33 women and 3 men aged 18 to 75 years; skin score 8.1 ± 3.1), of whom 20 had CREST syndrome since at least 4 of the 5 CREST features were observed during

Antiendothelial Cell Activity

In the global test, the mean BI of AECA (Fig. 1) were 6.9 ± 5.9% in the normal controls, 20.2 ± 12.4% in the patients with PRP (P = 0.0001, compared with the controls), 34.9 ± 20.1% in those with lSSc (P = 0.032, compared with the PRP patients), and 52.4 ± 28.6% in those with dSSc (P = 0.0078, compared with the lSSc patients). Assuming that the cut-off value is 24.6% (mean of normal controls +3 SD), AECA were found to be present in 3 patients with PRP (23%; 5 patients, 38%, were positive if 2

Discussion

The reduction of ACE activity is not a very sensitive indicator of immunological injury to the endothelium in SSc, possibly because of differences in the alleles of the ACE gene.[27] As discussed in depth by Blann et al,[24] circulating vWfAg originates in the endothelium. Similarly, Tm, an EC-specific glycoprotein, is liberated by damage to these cells. We have therefore examined plasma from patients with PRP, lSSc, and dSSc for evidence of EC injury, finding slightly reduced activity of ACE

Acknowledgements

We gratefully acknowledge Doctor Cora-Jean S. Edgell (Chapel Hill, NC) for generously providing the EA.hy926 and A549/8 cells. Thanks are also due to Doctor James B. Peter (Santa Monica, CA) and to Professor Peter M. Lydyard (London, UK) for their helpful comments, and to Mrs Annie Paul for her expert secretarial assistance.

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