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Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis.
Rheumatology (Oxford). 2004 Oct; 43(10):1261-6.R

Abstract

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.

Authors+Show Affiliations

Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. s-sato@med.kanazawa-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15266059

Citation

Sato, S, et al. "Serum Soluble CTLA-4 Levels Are Increased in Diffuse Cutaneous Systemic Sclerosis." Rheumatology (Oxford, England), vol. 43, no. 10, 2004, pp. 1261-6.
Sato S, Fujimoto M, Hasegawa M, et al. Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis. Rheumatology (Oxford). 2004;43(10):1261-6.
Sato, S., Fujimoto, M., Hasegawa, M., Komura, K., Yanaba, K., Hayakawa, I., Matsushita, T., & Takehara, K. (2004). Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis. Rheumatology (Oxford, England), 43(10), 1261-6.
Sato S, et al. Serum Soluble CTLA-4 Levels Are Increased in Diffuse Cutaneous Systemic Sclerosis. Rheumatology (Oxford). 2004;43(10):1261-6. PubMed PMID: 15266059.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis. AU - Sato,S, AU - Fujimoto,M, AU - Hasegawa,M, AU - Komura,K, AU - Yanaba,K, AU - Hayakawa,I, AU - Matsushita,T, AU - Takehara,K, Y1 - 2004/07/20/ PY - 2004/7/22/pubmed PY - 2004/11/2/medline PY - 2004/7/22/entrez SP - 1261 EP - 6 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 43 IS - 10 N2 - 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. SN - 1462-0324 UR - https://www.unboundmedicine.com/medline/citation/15266059/Serum_soluble_CTLA_4_levels_are_increased_in_diffuse_cutaneous_systemic_sclerosis_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/keh303 DB - PRIME DP - Unbound Medicine ER -