Skip to main content

Advertisement

SpringerLink
Log in

Increased circulating fibrinogen-like protein 2 in patients with systemic sclerosis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Fibrinogen-like protein 2 (FGL2), a member of the fibrinogen-related superfamily of proteins, is expressed on the surface of macrophages, T cells, and endothelial cells and directly cleaves prothrombin to thrombin. The aim of this study is to determine the serum FGL2 level and its association with clinical parameters in patients with systemic sclerosis (SSc). Serum FGL2 level was examined by enzyme-linked immunosorbent assay in 61 patients with SSc, 24 patients with systemic lupus erythematosus, and 24 healthy individuals. In a retrospective longitudinal study, sera from 13 patients with SSc were analyzed. The serum FGL2 level was increased in patients with SSc compared with healthy individuals (P < 0.001) and patients with systemic lupus erythematosus (P < 0.01). Among patients with SSc, there were no differences in serum FGL2 level between limited cutaneous SSc and diffuse cutaneous SSc. In the longitudinal study, the FGL2 level was generally unchanged at follow-up. The results show that the serum FGL2 level was increased in patients with SSc but not in patients with systemic lupus erythematosus or healthy individuals. Therefore, FGL2 possibly contribute to the development of SSc.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. White B (1996) Immunopathogenesis of systemic sclerosis. Rheum Dis Clin North Am 32:695–708

    Article  Google Scholar 

  2. Okano Y (1996) Antinuclear antibody in systemic sclerosis (scleroderma). Rheum Dis Clin North Am 22:709–735

    Article  PubMed  CAS  Google Scholar 

  3. Fleischmajer R, Perlish JS, Reeves JRT (1977) Cellular infiltrates in scleroderma skin. Arthritis Rheum 20:975–984

    Article  PubMed  CAS  Google Scholar 

  4. Scharffetter K, Lankat-Buttgereit B, Krieg T (1988) Localization of collagen mRNA in normal and scleroderma skin by in-situ hybridization. Eur J Clin Invest 18:9–17

    Article  PubMed  CAS  Google Scholar 

  5. Hasegawa M, Sato S (2008) The roles of chemokines in leukocyte recruitment and fibrosis in systemic sclerosis. Front Biosci 13:3637–3647

    Article  PubMed  CAS  Google Scholar 

  6. Koyama T, Hall LR, Haser WG, Tonegawa S, Saito H (1987) Structure of a cytotoxic T-lymphocyte-specific gene shows a strong homology to fibrinogen beta and gamma chains. Proc Natl Acad Sci USA 84:1609–1613

    Article  PubMed  CAS  Google Scholar 

  7. Ghanekar A, Mendicino M, Liu H et al (2004) Endothelial induction of fgl2 contributes to thrombosis during acute vascular xenograft rejection. J Immunol 172:5693–5701

    PubMed  CAS  Google Scholar 

  8. Marazzi S, Blum S, Hartmann R et al (1998) Characterization of human fibroleukin, a fibrinogen-like protein secreted by T lymphocytes. J Immunol 161:138–147

    PubMed  CAS  Google Scholar 

  9. Ning Q, Sun Y, Han M et al (2005) Role of fibrinogen-like protein 2 prothrombinase/fibroleukin in experimental and human allograft rejection. J Immunol 174:7403–7411

    PubMed  CAS  Google Scholar 

  10. Marsden PA, Ning Q, Fung LS et al (2003) The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis. J Clin Invest 112:58–66

    PubMed  CAS  Google Scholar 

  11. Li C, Fung LS, Chung S et al (1992) Monoclonal antiprothrombinase (3D4.3) prevents mortality from murine hepatitis virus (MHV-3) infection. J Exp Med 176:689–697

    Article  PubMed  CAS  Google Scholar 

  12. Melnyk MC, Shalev I, Zhang J et al (2011) The prothrombinase activity of FGL2 contributes to the pathogenesis of experimental arthritis. Scand J Rheumatol 40:269–278

    Article  PubMed  CAS  Google Scholar 

  13. Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590

    Article  Google Scholar 

  14. LeRoy EC, Krieg T, Black C et al (1988) Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis. J Rheumatol 15:202–205

    PubMed  CAS  Google Scholar 

  15. Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    Article  PubMed  CAS  Google Scholar 

  16. Steen VD, Powell DL, Medsger TAJ (1988) Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. Arthritis Rheum 31:196–203

    Article  PubMed  CAS  Google Scholar 

  17. Sato S, Ihn H, Kikuchi K, Takehara K (1994) Antihistone antibodies in systemic sclerosis: association with pulmonary fibrosis. Arthritis Rheum 37:391–394

    Article  PubMed  CAS  Google Scholar 

  18. Clements PJ, Lachenbruch PA, Seibold JR et al (1993) Skin thickness score in systemic sclerosis: an assessment of interobeservar variability in 3 independent studies. J Rheumatol 20:1892–1896

    PubMed  CAS  Google Scholar 

  19. Generini S, Matucci Cerinic M (1999) Raynaud’s phenomenon and vascular disease in systemic sclerosis. Adv Exp Med Biol 455:93–100

    Article  PubMed  CAS  Google Scholar 

  20. Suematsu M, Wakabayashi Y, Ishimura Y (1996) Gaseous monoxides: a new class of microvascular regulator in the liver. Cardiovasc Res 32:679–686

    PubMed  CAS  Google Scholar 

  21. Butler AR, Flitney FW, Williams DL (1995) NO, nitrosonium ions, nitroxide ions, nitrosothiols and iron-nitrosyls in biology: a chemist’s perspective. Trends Pharmacol Sci 16:18–22

    Article  PubMed  CAS  Google Scholar 

  22. Selzner N, Liu H, Boehnert MU et al (2012) FGL2/fibroleukin mediates hepatic reperfusion injury by induction of sinusoidal endothelial cell and hepatocyte apoptosis in mice. J Hepatol 56:153–159

    Article  PubMed  CAS  Google Scholar 

  23. Famularo G, Procopio A, Giacomelli R et al (1990) Soluble interleukin-2 receptor, interleukin-2 and interleukin-4 in sera and supernatants from patients with progressive systemic sclerosis. Clin Exp Immunol 81:368–372

    Article  PubMed  CAS  Google Scholar 

  24. Hasegawa M, Fujimoto M, Kikuchi K, Takehara K (1997) Elevated serum levels of interleukin 4 (IL-4), IL-10, and IL-13 in patients with systemic sclerosis. J Rheumatol 24:328–332

    PubMed  CAS  Google Scholar 

  25. Needleman BW, Wigley FM, Stair RW (1992) Interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor-a, and interferon-g levels in sera from patients with scleroderma. Arthritis Rheum 35:67–72

    Article  PubMed  CAS  Google Scholar 

  26. Matsushita T, Hasegawa M, Hamaguchi Y, Takehara K, Sato S (2006) Longitudinal analysis of serum cytokine concentrations in systemic sclerosis: association of interleukin 12 elevation with spontaneous regression of skin sclerosis. J Rheumatol 33:275–284

    PubMed  CAS  Google Scholar 

  27. Chan CW, Kay LS, Khadaroo RG et al (2003) Soluble fibrinogen-like protein 2/fibroleukin exhibits immunosuppressive properties: suppressing T cell proliferation and inhibiting maturation of bone marrow-derived dendritic cells. J Immunol 170:4036–4044

    PubMed  CAS  Google Scholar 

  28. Shalev I, Liu H, Koscik C et al (2008) Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis. J Immunol 180:249–260

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant for Research on Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan.

Disclosures

None.

Author information

Authors and Affiliations

  1. Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Koichi Yanaba, Yoshihide Asano, Shinji Noda, Kaname Akamata, Naohiko Aozasa, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono & Shinichi Sato

Authors
  1. Koichi Yanaba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshihide Asano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shinji Noda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaname Akamata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naohiko Aozasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takashi Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takehiro Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yohei Ichimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tetsuo Toyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hayakazu Sumida
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yoshihiro Kuwano
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yayoi Tada
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Makoto Sugaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Takafumi Kadono
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Shinichi Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Koichi Yanaba.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yanaba, K., Asano, Y., Noda, S. et al. Increased circulating fibrinogen-like protein 2 in patients with systemic sclerosis. Clin Rheumatol 32, 43–47 (2013). https://doi.org/10.1007/s10067-012-2089-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-012-2089-y

Keywords

Search

Navigation