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Elevated levels of serum MRP8/14 in ankylosing spondylitis: associated with peripheral arthritis and active disease

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Abstract

Monocytes of patients with ankylosing spondylitis (AS) have toll-like receptor 4 (TLR4) overexpression on their monocytes. Myeloid-related protein (MRP) 8/14 protein complexes are calcium-binding proteins, which act as endogenous ligands to TLR4. Thus, we studied the levels of MRP8/14 in adult AS patients. MRP8/14 levels were assessed in 99 adult AS patients satisfying Assessments in Ankylosing Spondylitis International Society 2010 criteria and 71 healthy controls by ELISA. Patient disease parameters like patient and physician global assessment, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), swollen and tender joint count, entheseal count by Maastricht enthesitis index, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were also recorded. Levels were reassessed in 23 patients after 2–5 months of treatment with NSAIDs. All values are in median (IQR). The serum MRP8/14 levels in patients [34.1 (17.94–264.58) μg/ml] were significantly higher than in healthy controls [4.94 (IQR 3.01–8.32) μg/ml (p < 0.0001)]. Patients with peripheral arthritis (n = 50) had higher levels than those with pure axial disease (n = 49) [40.63 (IQR 28.41–73.15) μg/ml vs. 23.72 (11.04–61.55) μg/ml; p = 0.012]. Levels of MRP8/14 correlated with AS Disease Activity Score (DAS)-CRP (r = 0.23, 95%CI = 0.038–0.422, p = 0.02) and CRP (r = 0.28, 95%CI = 0.081–0.45, p = 0.01), and the correlation was better in early disease [≤5 years disease duration; r = 0.40, p = 0.007 and r = 0.57, p = <0.0001, respectively]. Baseline levels were higher in treatment responders than in non-responders [51.17 vs. 32.22 μg/ml; p = 0.02]. Change in MRP8/14 levels correlated with change in BASDAI and ASDAS-CRP (r = 0.489, p = 0.018 and r = 0·498, p = 0.016, respectively). MRP8/14 levels may be used as a biomarker for activity, peripheral arthritis, and response to therapy.

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References

  1. Spoorenberg A, van Tubergen A, Landewé R, Dougados M, van der Linden S, Mielants H et al (2005) Measuring disease activity in ankylosing spondylitis: patient and physician have different perspectives. Rheumatology (Oxford) 44:789–795

    Article  CAS  Google Scholar 

  2. Robinson WH, Lindstrom TM, Cheung RK, Sokolove J (2013) Mechanistic biomarkers for clinical decision making in rheumatic diseases. Nat Rev Rheumatol 9:267–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D et al (2013) Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet 382:1705–1713

    Article  CAS  PubMed  Google Scholar 

  4. Smith JA (2016) The role of the unfolded protein response in axial spondyloarthritis. Clin Rheumatol 35:1425–1431

    Article  PubMed  Google Scholar 

  5. Zeng L, Lindstrom MJ, Smith JA (2011) Ankylosing spondylitis macrophage production of higher levels of interleukin-23 in response to lipopolysaccharide without induction of a significant unfolded protein response. Arthritis Rheum 63:3807–3817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Oktayoglu P, Bozkurt M, Mete N, Caglayan M, Em S, Nas K (2014) Elevated serum levels of calprotectin (myeloid-related protein 8/14) in patients with ankylosing spondylitis and its association with disease activity and quality of life. J Investig Med 62:880–884

    Article  CAS  PubMed  Google Scholar 

  7. Shukla A, Gaur P, Aggarwal A (2015) Tenascin-C levels, a toll-like receptor 4 ligand, in enthesitis-related arthritis category of juvenile idiopathic arthritis: a cross-sectional and longitudinal study. J Rheumatol 42:891–896

    Article  CAS  PubMed  Google Scholar 

  8. Liaunardy-Jopeace A, Gay NJ (2014) Molecular and cellular regulation of toll-like receptor-4 activity induced by lipopolysaccharide ligands. Front Immunol 5:473

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cypers H, Varkas G, Beeckman S, Debusschere K, Vogl T, Roth J et al (2016) Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis. Ann Rheum Dis 75:1357–1362

    Article  CAS  PubMed  Google Scholar 

  10. Turina MC, Yeremenko N, Paramarta JE, De Rycke L, Baeten D (2014) Calprotectin (S100A8/9) as serum biomarker for clinical response in proof-of-concept trials in axial and peripheral spondyloarthritis. Arthritis Res Ther 16:413

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rudwaleit M, Taylor WJ (2010) Classification criteria for psoriatic arthritis and ankylosing spondylitis/axial spondyloarthritis. Best Pract Res Clin Rheumatol 24:589–604

    Article  PubMed  Google Scholar 

  12. Rahman MT, Myles A, Gaur P, Misra R, Aggarwal A (2014) TLR4 endogenous ligand MRP8/14 level in enthesitis-related arthritis and its association with disease activity and TLR4 expression. Rheumatology (Oxford) 53:270–274

    Article  CAS  Google Scholar 

  13. Patro PS, Singh A, Misra R, Aggarwal A (2016) Myeloid-related protein 8/14 levels in rheumatoid arthritis: marker of disease activity and response to methotrexate. J Rheumatol 43:731–737

    Article  PubMed  Google Scholar 

  14. Hansson C, Eriksson C, Alenius G-M (2014) S-calprotectin (S100A8/S100A9): a potential marker of inflammation in patients with psoriatic arthritis. J Immunol Res 2014:696415

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kruithof E, De Rycke L, Vandooren B, De Keyser F, FitzGerald O, McInnes I et al (2006) Identification of synovial biomarkers of response to experimental treatment in early-phase clinical trials in spondylarthritis. Arthritis Rheum 54:1795–1804

    Article  CAS  PubMed  Google Scholar 

  16. Klingberg E, Carlsten H, Hilme E, Hedberg M, Forsblad-d’Elia H (2012) Calprotectin in ankylosing spondylitis—frequently elevated in feces, but normal in serum. Scand J Gastroenterol 47:435–444

    Article  CAS  PubMed  Google Scholar 

  17. Dekker-Saeys BJ, Meuwissen SG, Van Den Berg-Loonen EM, De Haas WH, Agenant D, Tytgat GN (1978) Ankylosing spondylitis and inflammatory bowel disease. II. Prevalence of peripheral arthritis, sacroiliitis, and ankylosing spondylitis in patients suffering from inflammatory bowel disease. Ann Rheum Dis 37:33–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Duran A, Kobak S, Sen N, Aktakka S, Atabay T, Orman M (2016) Fecal calprotectin is associated with disease activity in patients with ankylosing spondylitis. Bosn J Basic Med Sci 16:71–74

    PubMed  PubMed Central  Google Scholar 

  19. Pedersen SJ, Sørensen IJ, Hermann K-GA, Madsen OR, Tvede N, Hansen MS et al (2010) Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical and MRI measures of disease activity in a 1-year follow-up study of patients with axial spondyloarthritis treated with tumour necrosis factor alpha inhibitors. Ann Rheum Dis 69:1065–1071

    Article  PubMed  Google Scholar 

  20. van der Heijde D, Lie E, Kvien TK, Sieper J, Van den Bosch F, Listing J et al (2009) ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis 68:1811–1818

    Article  PubMed  Google Scholar 

  21. Spoorenberg A, van der Heijde D, de Klerk E, Dougados M, de Vlam K, Mielants H et al (1999) A comparative study of the usefulness of the Bath Ankylosing Spondylitis Functional Index and the Dougados Functional Index in the assessment of ankylosing spondylitis. J Rheumatol 26:961–965

    CAS  PubMed  Google Scholar 

  22. Ramiro S, Stolwijk C, van Tubergen A, van der Heijde D, Dougados M, van den Bosch F et al (2015) Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective follow-up of the OASIS study. Ann Rheum Dis 74:52–59

    Article  PubMed  Google Scholar 

  23. Baraliakos X, Listing J, Rudwaleit M, Haibel H, Brandt J, Sieper J et al (2007) Progression of radiographic damage in patients with ankylosing spondylitis: defining the central role of syndesmophytes. Ann Rheum Dis 66:910–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Choi IY, Gerlag DM, Herenius MJ, Thurlings RM, Wijbrandts CA, Foell D et al (2015) MRP8/14 serum levels as a strong predictor of response to biological treatments in patients with rheumatoid arthritis. Ann Rheum Dis 74:499–505

    Article  CAS  PubMed  Google Scholar 

  25. Tibble J, Sigthorsson G, Foster R, Scott D, Fagerhol M, Roseth A et al (1999) High prevalence of NSAID enteropathy as shown by a simple faecal test. Gut 45:362–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India

    Latika Gupta, Shruti Bhattacharya, Vikas Agarwal & Amita Aggarwal

Authors
  1. Latika Gupta
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  2. Shruti Bhattacharya
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  3. Vikas Agarwal
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  4. Amita Aggarwal
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Corresponding author

Correspondence to Amita Aggarwal.

Ethics declarations

The study was conducted at Sanjay Gandhi Postgraduate Institute, Lucknow, and was approved by the institutional ethics committee (2015–65-DM-EXP; 06/Apr/15). All patients of AS who were seen in the outpatient from May 2015 to December 2015 were informed about the study and included if they gave consent.

Funding statement

Project was partly supported by a grant from Department of Science and Technology to AA. SB was supported by a Junior Research Fellowship from Department of Biotechnology, Government of India.

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Gupta, L., Bhattacharya, S., Agarwal, V. et al. Elevated levels of serum MRP8/14 in ankylosing spondylitis: associated with peripheral arthritis and active disease. Clin Rheumatol 35, 3075–3079 (2016). https://doi.org/10.1007/s10067-016-3448-x

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  • DOI: https://doi.org/10.1007/s10067-016-3448-x

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