Skip to main content

Advertisement

SpringerLink
Log in

Elevated high-mobility group B1 levels in active adult-onset Still’s disease associated with systemic score and skin rash

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

Abstract

High-mobility group box-1 (HMGB1) is a nuclear protein, and such prototypical damage-associated molecular patterns mediate the immune response in the noninfectious inflammatory response. Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder involved in the dysregulation of innate immunity. We investigated the serum HMGB1 level in patients with AOSD and evaluated its clinical significance. Blood samples were collected from 40 patients with active AOSD and 40 healthy controls (HC). Of the patients with AOSD, follow-up samples were collected from 16 patients after a resolution of AOSD disease activity. Serum HMGB1 levels in patients with AOSD were higher than those of the HC (10.0 ± 5.85 vs. 5.15 ± 1.79 ng/mL, p < 0.001). Serum HMGB1 levels were found to be correlated with C-reactive protein (CRP) and the systemic score. The AOSD patient who had a sore throat showed a higher serum HMGB1 level than those patients who did not, and the patient with a skin rash had higher levels than the patients without. In addition, the serum HMGB1 levels were decreased after the resolution of disease activity in the AOSD patients who were followed up. The serum HMGB1 levels were elevated in AOSD patients compared to the HC and were correlated with both CRP and the systemic score. The HMGB1 levels were associated with skin rash and a sore throat in AOSD patients. After the resolution of disease activity, serum HMGB1 levels were found to have decreased.

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. Bywaters EG (1971) Still’s disease in the adult. Ann Rheum Dis 30:121–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ohta A, Yamaguchi M, Tsunematsu T, Kasukawa R, Mizushima H, Kashiwagi H, Kashiwazaki S, Tanimoto K, Matsumoto Y, Akizuki M et al (1990) Adult Still’s disease: a multicenter survey of Japanese patients. J Rheumatol 17:1058–1063

    CAS  PubMed  Google Scholar 

  3. Kim HA, Sung JM, Suh CH (2012) Therapeutic responses and prognosis in adult-onset Still’s disease. Rheumatol Int 32:1291–1298

    Article  CAS  PubMed  Google Scholar 

  4. Efthimiou P, Kontzias A, Ward CM, Ogden NS (2007) Adult-onset Still’s disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy? Nat Clin Pract Rheumatol 3:328–335

    Article  CAS  PubMed  Google Scholar 

  5. Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Seve P (2014) Adult-onset Still’s disease. Autoimmun Rev 13:708–722

    Article  CAS  PubMed  Google Scholar 

  6. Kim HA, Kwon JE, Yim H, Suh CH, Jung JY, Han JH (2015) The pathologic findings of skin, lymph node, liver, and bone marrow in patients with adult-onset still disease: a comprehensive analysis of 40 cases. Medicine (Baltimore) 94:e787

    Article  Google Scholar 

  7. Kumar S, Kunhiraman DS, Rajam L (2012) Application of the Yamaguchi criteria for classification of “suspected” systemic juvenile idiopathic arthritis (sJIA). Pediatr Rheumatol Online J 10:40

    Article  PubMed  PubMed Central  Google Scholar 

  8. Jamilloux Y, Gerfaud-Valentin M, Martinon F, Belot A, Henry T, Seve P (2015) Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart. Immunol Res 61:53–62

    Article  CAS  PubMed  Google Scholar 

  9. Bagnari V, Colina M, Ciancio G, Govoni M, Trotta F (2010) Adult-onset Still’s disease. Rheumatol Int 30:855–862

    Article  CAS  PubMed  Google Scholar 

  10. Chen DY, Lan JL, Lin FJ, Hsieh TY (2004) Proinflammatory cytokine profiles in sera and pathological tissues of patients with active untreated adult onset Still’s disease. J Rheumatol 31:2189–2198

    CAS  PubMed  Google Scholar 

  11. Han JH, Suh CH, Jung JY, Nam JY, Kwon JE, Yim H, Kim HA (2015) Association of CXCL10 and CXCL13 levels with disease activity and cutaneous manifestation in active adult-onset Still’s disease. Arthritis Res Ther 17:260

    Article  PubMed  PubMed Central  Google Scholar 

  12. Andersson U, Antoine DJ, Tracey KJ (2014) The functions of HMGB1 depend on molecular localization and post-translational modifications. J Intern Med 276:420–424

    Article  CAS  PubMed  Google Scholar 

  13. Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A (2008) HMGB1: endogenous danger signaling. Mol Med 14:476–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Harris HE, Andersson U, Pisetsky DS (2012) HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol 8:195–202

    Article  CAS  PubMed  Google Scholar 

  15. Wahamaa H, Schierbeck H, Hreggvidsdottir HS, Palmblad K, Aveberger AC, Andersson U, Harris HE (2011) High mobility group box protein 1 in complex with lipopolysaccharide or IL-1 promotes an increased inflammatory phenotype in synovial fibroblasts. Arthritis Res Ther 13:R136

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lu M, Yu S, Xu W, Gao B, Xiong S (2015) HMGB1 promotes systemic lupus erythematosus by enhancing macrophage inflammatory response. J Immunol Res 2015:946748

    Article  PubMed  PubMed Central  Google Scholar 

  17. Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, Kashiwazaki S, Tanimoto K, Matsumoto Y, Ota T et al (1992) Preliminary criteria for classification of adult Still’s disease. J Rheumatol 19:424–430

    CAS  PubMed  Google Scholar 

  18. Pouchot J, Sampalis JS, Beaudet F, Carette S, Decary F, Salusinsky-Sternbach M, Hill RO, Gutkowski A, Harth M, Myhal D et al (1991) Adult Still’s disease: manifestations, disease course, and outcome in 62 patients. Medicine (Baltimore) 70:118–136

    Article  CAS  Google Scholar 

  19. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581

    Article  PubMed  Google Scholar 

  20. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O et al (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kim HA, An JM, Nam JY, Jeon JY, Suh CH (2012) Serum S100A8/A9, but not follistatin-like protein 1 and interleukin 18, may be a useful biomarker of disease activity in adult-onset Still’s disease. J Rheumatol 39:1399–1406

    Article  CAS  PubMed  Google Scholar 

  22. Bae CB, Suh CH, An JM, Jung JY, Jeon JY, Nam JY, Kim HA (2014) Serum S100A12 may be a useful biomarker of disease activity in adult-onset Still’s disease. J Rheumatol 41:2403–2408

    Article  PubMed  Google Scholar 

  23. Wittkowski H, Frosch M, Wulffraat N, Goldbach-Mansky R, Kallinich T, Kuemmerle-Deschner J, Fruhwald MC, Dassmann S, Pham TH, Roth J et al (2008) S100A12 is a novel molecular marker differentiating systemic-onset juvenile idiopathic arthritis from other causes of fever of unknown origin. Arthritis Rheum 58:3924–3931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Andersson U, Tracey KJ (2011) HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol 29:139–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu G, Wang J, Park YJ, Tsuruta Y, Lorne EF, Zhao X, Abraham E (2008) High mobility group protein-1 inhibits phagocytosis of apoptotic neutrophils through binding to phosphatidylserine. J Immunol 181:4240–4246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chen Y, Sun W, Gao R, Su Y, Umehara H, Dong L, Gong F (2013) The role of high mobility group box chromosomal protein 1 in rheumatoid arthritis. Rheumatology (Oxford) 52:1739–1747

    Article  CAS  Google Scholar 

  27. Jiang W, Pisetsky DS (2007) Mechanisms of disease: the role of high-mobility group protein 1 in the pathogenesis of inflammatory arthritis. Nat Clin Pract Rheumatol 3:52–58

    Article  CAS  PubMed  Google Scholar 

  28. Taniguchi N, Kawahara K, Yone K, Hashiguchi T, Yamakuchi M, Goto M, Inoue K, Yamada S, Ijiri K, Matsunaga S et al (2003) High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum 48:971–981

    Article  CAS  PubMed  Google Scholar 

  29. Guo HF, Liu SX, Zhang YJ, Liu QJ, Hao J, Gao LX (2011) High mobility group box 1 induces synoviocyte proliferation in rheumatoid arthritis by activating the signal transducer and activator transcription signal pathway. Clin Exp Med 11:65–74

    Article  CAS  PubMed  Google Scholar 

  30. Kokkola R, Li J, Sundberg E, Aveberger AC, Palmblad K, Yang H, Tracey KJ, Andersson U, Harris HE (2003) Successful treatment of collagen-induced arthritis in mice and rats by targeting extracellular high mobility group box chromosomal protein 1 activity. Arthritis Rheum 48:2052–2058

    Article  CAS  PubMed  Google Scholar 

  31. Schierbeck H, Pullerits R, Pruunsild C, Fischer M, Holzinger D, Laestadius A, Sundberg E, Harris HE (2013) HMGB1 levels are increased in patients with juvenile idiopathic arthritis, correlate with early onset of disease, and are independent of disease duration. J Rheumatol 40:1604–1613

    Article  CAS  PubMed  Google Scholar 

  32. Bobek D, Grcevic D, Kovacic N, Lukic IK, Jelusic M (2014) The presence of high mobility group box-1 and soluble receptor for advanced glycation end-products in juvenile idiopathic arthritis and juvenile systemic lupus erythematosus. Pediatr Rheumatol Online J 12:50

    Article  PubMed  PubMed Central  Google Scholar 

  33. Chen T, Guo ZP, Li L, Wang L, Jia RZ, Cao N, Qin S, Li MM (2013) Increased HMGB1 serum levels and altered HMGB1 expression in patients with psoriasis vulgaris. Arch Dermatol Res 305:263–267

    Article  CAS  PubMed  Google Scholar 

  34. Abdulahad DA, Westra J, Reefman E, Zuidersma E, Bijzet J, Limburg PC, Kallenberg CG, Bijl M (2013) High mobility group box1 (HMGB1) in relation to cutaneous inflammation in systemic lupus erythematosus (SLE). Lupus 22:597–606

    Article  CAS  PubMed  Google Scholar 

  35. Andersson U, Harris HE (2010) The role of HMGB1 in the pathogenesis of rheumatic disease. Biochim Biophys Acta 1799:141–148

    Article  CAS  PubMed  Google Scholar 

  36. Bae JS (2012) Role of high mobility group box 1 in inflammatory disease: focus on sepsis. Arch Pharm Res 35:1511–1523

    Article  CAS  PubMed  Google Scholar 

  37. Goldstein RS (2008) High mobility group box-1 protein as a tumor necrosis factor-independent therapeutic target in rheumatoid arthritis. Arthritis Res Ther 10:111

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This research was supported by the M.D., Ph.D. research fund of Ajou University School of Medicine (M2014C046000129).

Author information

Authors and Affiliations

  1. Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Korea

    Ju-Yang Jung, Chang-Hee Suh, Jin-Young Nam & Hyoun-Ah Kim

  2. Department of Microbiology, Ajou University School of Medicine, Yeongtong-gu, Suwon, Korea

    Seonghyang Sohn

Authors
  1. Ju-Yang Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chang-Hee Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seonghyang Sohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jin-Young Nam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyoun-Ah Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hyoun-Ah Kim.

Ethics declarations

Disclosures

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jung, JY., Suh, CH., Sohn, S. et al. Elevated high-mobility group B1 levels in active adult-onset Still’s disease associated with systemic score and skin rash. Clin Rheumatol 35, 1937–1942 (2016). https://doi.org/10.1007/s10067-016-3314-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-016-3314-x

Keywords

Search

Navigation