Rheumatology Advance Access originally published online on July 20, 2004
Rheumatology 2004 43(10):1261-1266; doi:10.1093/rheumatology/keh303
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Rheumatology Vol. 43 No. 10 © British Society for Rheumatology 2004; all rights reserved
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Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa and 1 Department of Regenerative Medicine, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Correspondence to: S. Sato, Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13–1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. E-mail: s-sato{at}med.kanazawa-u.ac.jp
Objective. To determine serum levels of soluble cytotoxic T-lymphocyte associated molecule-4 (sCTLA-4) and clinical association in patients with systemic sclerosis (SSc).
Methods. Serum sCTLA-4 levels from 32 patients with diffuse cutaneous SSc (dSSc) and 27 patients with limited cutaneous SSc (lSSc) were examined by enzyme-linked immunosorbent assay (ELISA). For a longitudinal study, 211 sera from 30 SSc patients were analysed (follow-up 2.1–7.0 yr).
Results. Serum sCTLA-4 levels were elevated in dSSc patients compared with normal controls (n = 41), lSSc patients and patients with active systemic lupus erythematosus (SLE) (n = 23). By contrast, sCTLA-4 levels in patients with lSSc or SLE were normal. SSc patients with elevated sCTLA-4 levels had a shorter disease duration and more frequent presence of digital pitting scars, contracture of phalanges, diffuse pigmentation, pulmonary fibrosis and decreased percentage vital capacity (%VC) than those with normal sCTLA-4 levels. sCTLA-4 levels correlated positively with the extent of skin fibrosis, serum IgG levels and anti-topoisomerase I antibody levels. In a longitudinal study, sCTLA-4 levels decreased on a parallel with improvement of skin sclerosis in five dSSc patients. Skin sclerosis did not improve in two of six dSSc patients with high sCTLA-4 levels throughout the follow-up, while the remaining four patients showed improvement of skin sclerosis.
Conclusion. These results suggest that sCTLA-4 correlates with disease severity and activity of SSc and that sCTLA-4 plays a role in immunological abnormalities of SSc, since sCTLA-4 may augment humoral immune responses as well as T-cell responses by interfering with B7-CTLA-4 interactions that induce negative signals in T and B cells.
KEY WORDS: Cytotoxic T-lymphocyte associated molecule-4, Soluble form, Diffuse cutaneous systemic sclerosis, Autoantibody