ab22404

Anti-endothelial cell antibodies in mixed connective tissue disease: Frequency and association with clinical symptoms

E. Bodolay¹, I. Csipo², I. Gál^1,3, S. Sipka², E. Gyimesi², Z. Szekanecz³, G. Szegedi¹

Divisions of ¹Clinical Immunology and ³Rheumatology, and the ²Regional Immunology Laboratory, 3rd Department of Internal Medicine, University Debrecen, Medical and Health Science Center, Debrecen, Hungary

ABSTRACT
Objective
Anti-endothelial cell antibodies (AECA) have been described in a number of systemic autoimmune-inflammatory diseases. However, little is known about the relationship of AECA with mixed connective tissue disease (MCTD).

Methods
Using an ELISA, the presence of AECA was evaluated in the sera of 33 patients with MCTD and of 30 healthy subjects as controls. Serum levels of AECA were correlated with clinical activity, as well as the existence of various organ manifestations.

Results
Significantly increased AECA production was observed in MCTD patients (OD = 0.337 ± 0.193) compared to controls (OD = 0.136 ± 0.065). In addition, patients with active MCTD exerted significantly elevated serum AECA levels (OD = 0.487 ± 0.090) than did patients with inactive MCTD (OD = 0.135 ± 0.040) or controls. MCTD patients with pulmonary hypertension had a tendency of increased serum AECA levels (OD = 0.452 ± 0.080) compared to patients without this manifestation (OD = 0.307 ± 0.039). Sera of MCTD patients with AECA concentrations higher or lower than the mean serum AECA level in controls+2SD (OD = 0.266) were considered as AECA^high (n = 19/33) and AECA^low (n = 14/33), respectively. Interestingly, all patients with active disease had AECA^high, while all inactive MCTD patients had AECA^low sera. IgG purified from ten MCTD sera (OD = 0.415 ± 0.290) showed a tendency to up-regulate E-selectin expression on cultured human umbilical vein endothelial cells (HUVEC) compared to IgG from control sera. In addition, AECA^high MCTD sera exerted significantly increased stimulatory effect on endothelial E-selectin expression (OD = 0.651 ± 0.190) compared to AECA^low (OD = 0.178 ± 0.110) or control sera (OD = 0.131 ± 0.080).

Conclusion
AECA may activate endothelial cells by the up-regulation of E-selectin expression and thus may be implicated in the pathogenesis of MCTD. Furthermore, serum AECA may be a useful marker of endothelial activation and clinical activity in this disease.

Key words
Anti-endothelial cell antibodies, mixed connective tissue disease, disease activity.

This work was supported by grant F 025813 from the Hungarian National Scientific Research Fund (OTKA) (Z.S.), grant No 0018 from the Research and Development Fund for Highest Education (FKFP) (Z.S), and grants No. 60/2000 and 60/2001 (Z.S.) and grant No. 417/2003 (B.E.) from the Medical Research Council (ETT).
Please address correspondence and reprint requests to: Edit Bodolay MD, Ph.D, Division of Clinical Immunology, 3rd Department of Internal Medicine, University of Debrecen, Medical and Health Science Center, Móricz Zs. krt. 22, H-4004 Debrecen, Hungary.
E-mail: bodolai@iiibel.dote.hu