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Increased production of soluble inducible costimulator in patients with diffuse cutaneous systemic sclerosis

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Abstract

Inducible costimulator (ICOS) is crucial for T cell proliferation, production of various cytokines, and T cell-dependent B-cell responses. To determine the serum soluble ICOS (sICOS) level and its association with clinical parameters in patients with systemic sclerosis (SSc), serum sICOS level was examined by enzyme-linked immunosorbent assay in 38 patients with SSc and 24 healthy individuals. The expression of ICOS and ICOS ligand in skin was examined immunohistochemically. There was no significant difference in serum sICOS level between patients with SSc and healthy individuals. Patients with diffuse cutaneous SSc had higher levels of sICOS than those with limited cutaneous SSc (P < 0.05) or healthy individuals (P < 0.05). Serum sICOS level correlated positively with the severity of skin sclerosis. Patients with SSc and elevated sICOS level more often had interstitial lung disease and decreased vital capacity than those with normal sICOS level. The serum sICOS level was significantly greater in patients with early phase SSc than those with late phase SSc. ICOS and ICOS ligand immunostaining were observed on infiltrating dermal mononuclear cells in lesional skin tissue. These results suggest that the serum level of sICOS is increased in patients with diffuse cutaneous SSc and correlates with the severity and activity of skin sclerosis and interstitial lung disease. ICOS may contribute to the development of SSc. In addition, measurement of serum sICOS level in patients with early SSc may offer an important means for further evaluation of SSc disease severity.

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References

  1. Akiba H, Takeda K, Kojima Y et al (2005) The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo. J Immunol 175:2340–2348

    PubMed  CAS  Google Scholar 

  2. Breitfeld D, Ohl L, Kremmer E et al (2000) Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 192:1545–1552

    Article  PubMed  CAS  Google Scholar 

  3. 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 

  4. Coyle AJ, Lehar S, Lloyd C et al (2000) The CD28-related molecule ICOS is required for effective T cell-dependent immune responses. Immunity 13:95–105

    Article  PubMed  CAS  Google Scholar 

  5. Ding H, Wu X, Wu J et al (2006) Delivering PD-1 inhibitory signal concomitant with blocking ICOS co-stimulation suppresses lupus-like syndrome in autoimmune BXSB mice. Clin Immunol 118:258–267

    Article  PubMed  CAS  Google Scholar 

  6. Dong C, Juedes AE, Temann UA et al (2001) ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 409:97–101

    Article  PubMed  CAS  Google Scholar 

  7. Famularo G, Giacomelli R, Alesse E et al (1989) Polyclonal B lymphocyte activation in progressive systemic sclerosis. J Clin Lab Immunol 29:59–63

    PubMed  CAS  Google Scholar 

  8. 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 

  9. Frey O, Meisel J, Hutloff A et al (2010) Inducible costimulator (ICOS) blockade inhibits accumulation of polyfunctional T helper 1/T helper 17 cells and mitigates autoimmune arthritis. Ann Rheum Dis 69:1495–1501

    Article  PubMed  CAS  Google Scholar 

  10. 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 

  11. Hutloff A, Buchner K, Reiter K et al (2004) Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus. Arthritis Rheum 50:3211–3220

    Article  PubMed  Google Scholar 

  12. Iwai H, Abe M, Hirose S et al (2003) Involvement of inducible costimulator-B7 homologous protein costimulatory pathway in murine lupus nephritis. J Immunol 171:2848–2854

    PubMed  CAS  Google Scholar 

  13. Iwai H, Kozono Y, Hirose S et al (2002) Amelioration of collagen-induced arthritis by blockade of inducible costimulator-B7 homologous protein costimulation. J Immunol 169:4332–4339

    PubMed  CAS  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. Liu Y, Zhu T, Cai G et al (2011) Elevated circulating CD4+ ICOS+ Foxp3+ T cells contribute to overproduction of IL-10 and are correlated with disease severity in patients with systemic lupus erythematosus. Lupus 20:620–627

    Article  PubMed  CAS  Google Scholar 

  16. Mak TW, Shahinian A, Yoshinaga SK et al (2003) Costimulation through the inducible costimulator ligand is essential for both T helper and B cell functions in T cell-dependent B cell responses. Nat Immunol 4:765–772

    Article  PubMed  CAS  Google Scholar 

  17. 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 

  18. McAdam AJ, Chang TT, Lumelsky AE et al (2000) Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4+ T cells. J Immunol 165:5035–5040

    PubMed  CAS  Google Scholar 

  19. McAdam AJ, Greenwald RJ, Levin MA et al (2001) ICOS is critical for CD40-mediated antibody class switching. Nature 409:102–105

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Nurieva RI, Duong J, Kishikawa H et al (2003) Transcriptional regulation of th2 differentiation by inducible costimulator. Immunity 18:801–811

    Article  PubMed  CAS  Google Scholar 

  22. Nurieva RI, Liu X, Dong C (2009) Yin-Yang of costimulation: crucial controls of immune tolerance and function. Immunol Rev 229:88–100

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. Sato S, Hamaguchi Y, Hasegawa M, Takehara K (2001) Clinical significance of anti-topoisomerase I antibody levels by ELISA in systemic sclerosis. Rheumatology 40:1135–1140

    Article  PubMed  CAS  Google Scholar 

  25. 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 

  26. Scott BG, Yang H, Tuzun E, Dong C, Flavell RA, Christadoss P (2004) ICOS is essential for the development of experimental autoimmune myasthenia gravis. J Neuroimmunol 153:16–25

    Article  PubMed  CAS  Google Scholar 

  27. 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 

  28. 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 

  29. Tafuri A, Shahinian A, Bladt F et al (2001) ICOS is essential for effective T-helper-cell responses. Nature 409:105–109

    Article  PubMed  CAS  Google Scholar 

  30. Tanaka C, Fujimoto M, Hamaguchi Y, Sato S, Takehara K, Hasegawa M (2010) Inducible costimulator ligand regulates bleomycin-induced lung and skin fibrosis in a mouse model independently of the inducible costimulator/inducible costimulator ligand pathway. Arthritis Rheum 62:1723–1732

    Article  PubMed  CAS  Google Scholar 

  31. Vinuesa CG, Tangye SG, Moser B, Mackay CR (2005) Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 5:853–865

    Article  PubMed  CAS  Google Scholar 

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

    Article  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.

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The authors have no conflicts of interest.

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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

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  1. Koichi Yanaba
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Correspondence to Koichi Yanaba.

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Yanaba, K., Asano, Y., Noda, S. et al. Increased production of soluble inducible costimulator in patients with diffuse cutaneous systemic sclerosis. Arch Dermatol Res 305, 17–23 (2013). https://doi.org/10.1007/s00403-012-1292-7

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  • DOI: https://doi.org/10.1007/s00403-012-1292-7

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