Skip to main content

Advertisement

Log in

Serum levels of soluble CD163 in patients with systemic sclerosis

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

Abstract

Macrophages may play a role in the pathogenesis of systemic sclerosis (SSc), and CD163-positive M2 macrophages are potentially important source for fibrosis-inducing cytokines. However, no link between M2 macrophages and SSc has been established. The aim is to evaluate the possibility that serum levels of soluble CD163 (sCD163) can be a useful marker for SSc, reflecting M2 activation of macrophages in this disease. Serum sCD163 levels of 43 patients with SSc, 10 patients with scleroderma spectrum disorder (SSD), and 12 healthy controls were measured with specific enzyme-linked immunosorbent assays. SSc patients had significantly higher serum sCD163 levels than healthy controls. The sCD163 levels in SSD patients were higher than healthy controls and lower than SSc patients. Significantly higher right ventricular systolic pressure and lower % DLco levels, and shorter duration of disease were seen in SSc patients with elevated serum sCD163 levels than those with normal levels. These results suggest that sCD163 levels may be increased in proportion to the progression of this disease, indicating the involvement of CD163 in the pathogenesis of SSc. Furthermore, serum sCD163 levels may be a marker of pulmonary hypertension at the early stage in patients with SSc.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Ishikawa O, Ishikawa H (1992) Macrophage infiltration in the skin of patients with systemic sclerosis. J Rheumatol 19:1202–1206

    PubMed  CAS  Google Scholar 

  2. Varga J (2004) Pathogenesis: emphasis on human data. In: Clements PJ (ed) Systemic sclerosis, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 63–97

    Google Scholar 

  3. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35

    Article  PubMed  CAS  Google Scholar 

  4. Higashi-Kuwata N, Makino T, Inoue Y, Takeya M, Ihn H (2009) Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma. Exp Dermatol 18:727–729

    Article  PubMed  Google Scholar 

  5. Mosser D (2003) The many faces of macrophage activation. J Leukoc Biol 73:209–212

    Article  PubMed  CAS  Google Scholar 

  6. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677–686

    Article  PubMed  CAS  Google Scholar 

  7. Komohara Y, Hirahara J, Horikawa T, Kawamura K, Kiyota E, Sakashita N et al (2006) AM-3 K, an anti-macrophage antibody, recognizes CD163, a molecule associated with an anti-inflammatory macrophage phenotype. J Histochem Cytochem 54:763–771

    Article  PubMed  CAS  Google Scholar 

  8. Martinez F, Gordon S, Locati M, Mantovani A (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 177:7303–7311

    PubMed  CAS  Google Scholar 

  9. Kodelja V, Müller C, Tenorio S, Schebesch C, Orfanos C, Goerdt S (1997) Differences in angiogenic potential of classically vs alternatively activated macrophages. Immunobiology 197:478–493

    Article  PubMed  CAS  Google Scholar 

  10. Raes G, Beschin A, Ghassabeh G, De Baetselier P (2007) Alternatively activated macrophages in protozoan infections. Curr Opin Immunol 19:454–459

    Article  PubMed  CAS  Google Scholar 

  11. Nielsen M, Madsen M, Møller H, Moestrup S (2006) The macrophage scavenger receptor CD163: endocytic properties of cytoplasmic tail variants. J Leukoc Biol 79:837–845

    Article  PubMed  CAS  Google Scholar 

  12. Raychaudhuri B, Bonfield T, Malur A, Hague K, Kavuru M, Arroliga A et al (2002) Circulating monocytes from patients with primary pulmonary hypertension are hyporesponsive. Clin Immunol 104:191–198

    Article  PubMed  CAS  Google Scholar 

  13. Sakkas L, Chikanza I, Platsoucas C (2006) Mechanisms of disease: the role of immune cells in the pathogenesis of systemic sclerosis. Nat Clin Pract Rheumatol 2:679–685

    Article  PubMed  CAS  Google Scholar 

  14. Maricq H, McGregor A, Diat F, Smith E, Maxwell D, LeRoy E et al (1990) Major clinical diagnoses found among patients with Raynaud phenomenon from the general population. J Rheumatol 17:1171–1176

    PubMed  CAS  Google Scholar 

  15. Baeten D, Møller H, Delanghe J, Veys E, Moestrup S, De Keyser F (2004) Association of CD163+ macrophages and local production of soluble CD163 with decreased lymphocyte activation in spondylarthropathy synovitis. Arthritis Rheum 50:1611–1623

    Article  PubMed  Google Scholar 

  16. Hiraoka A, Horiike N, Akbar S, Michitaka K, Matsuyama T, Onji M (2005) Soluble CD163 in patients with liver diseases: very high levels of soluble CD163 in patients with fulminant hepatic failure. J Gastroenterol 40:52–56

    Article  PubMed  CAS  Google Scholar 

  17. Kawamura K, Komohara Y, Takaishi K, Katabuchi H, Takeya M (2009) Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. Pathol Int 59:300–305

    Article  PubMed  Google Scholar 

  18. Matsushita N, Kashiwagi M, Wait R, Nagayoshi R, Nakamura M, Matsuda T et al (2002) Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3. Clin Exp Immunol 130:156–161

    Article  PubMed  CAS  Google Scholar 

  19. LeRoy E, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TJ et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205

    PubMed  CAS  Google Scholar 

  20. Ihn H, Sato S, Fujimoto M, Kikuchi K, Igarashi A, Soma Y et al (1996) Measurement of anticardiolipin antibodies by ELISA using β2-glycoprotein I (β 2-GPI) in systemic sclerosis. Clin Exp Immunol 105:475–479

    Article  PubMed  CAS  Google Scholar 

  21. Ihn H, Sato S, Tamaki T, Soma Y, Tsuchida T, Ishibashi Y et al (1992) Clinical evaluation of scleroderma spectrum disorders using a points system. Arch Dermatol Res 284:391–395

    Article  PubMed  CAS  Google Scholar 

  22. Maricq H, Weinrich M, Keil J, Smith E, Harper F, Nussbaum A et al (1989) Prevalence of scleroderma spectrum disorders in the general population of South Carolina. Arthritis Rheum 32:998–1006

    Article  PubMed  CAS  Google Scholar 

  23. Yamane K, Ihn H, Asano Y, Yazawa N, Kubo M, Kikuchi K et al (2000) Clinical and laboratory features of scleroderma patients with pulmonary hypertension. Rheumatology 39:1269–1271

    Article  PubMed  CAS  Google Scholar 

  24. Proudman S, Stevens W, Sahhar J, Celermajer D (2007) Pulmonary arterial hypertension in systemic sclerosis: the need for early detection and treatment. Intern Med J 37:485–494

    Article  PubMed  CAS  Google Scholar 

  25. Mathai S, Gulati M, Peng X, Russell T, Shaw A, Rubinowitz A et al. (2010) Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype. Lab Invest (in press)

  26. Sugita T, Stenmark K, Wagner WJ, Henson P, Henson J, Hyers T et al (1983) Abnormal alveolar cells in monocrotaline induced pulmonary hypertension. Exp Lung Res 5:201–215

    Article  PubMed  CAS  Google Scholar 

  27. Abe K, Shimokawa H, Morikawa K, Uwatoku T, Oi K, Matsumoto Y et al (2004) Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ Res 94:385–393

    Article  PubMed  CAS  Google Scholar 

  28. Jankov R, Luo X, Belcastro R, Copland I, Frndova H, Lye S et al (2001) Gadolinium chloride inhibits pulmonary macrophage influx and prevents O2-induced pulmonary hypertension in the neonatal rat. Pediatr Res 50:172–183

    Article  PubMed  CAS  Google Scholar 

  29. Denton C, Cailes J, Phillips G, Wells A, Black C, Bois R (1997) Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis. Br J Rheumatol 36:239–243

    Article  PubMed  CAS  Google Scholar 

  30. Sulahian T, Hintz K, Wardwell K, Guyre P (2001) Development of an ELISA to measure soluble CD163 in biological fluids. J Immunol Methods 252:25–31

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a grant for scientific research from the Japanese Ministry of Education, Science, Sports and Culture, by project research for progressive systemic sclerosis from the Japanese Ministry of Health and Welfare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Masatoshi Jinnin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakayama, W., Jinnin, M., Makino, K. et al. Serum levels of soluble CD163 in patients with systemic sclerosis. Rheumatol Int 32, 403–407 (2012). https://doi.org/10.1007/s00296-010-1691-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-010-1691-z

Keywords

Navigation