nach oben

Erschienen in:

22.04.2017 | Original Article

Correlation of serum MMP3 and other biomarkers with clinical outcomes in patients with ankylosing spondylitis: a pilot study

verfasst von: Dongyi He, Qi Zhu, Quan Zhou, Qing Qi, Hongmei Sun, Liza M. Zachariah, Grace Wang, John D. Reveille, Yongtao Guan, Xiaodong Zhou

Erschienen in: Clinical Rheumatology | Ausgabe 8/2017

Einloggen, um Zugang zu erhalten

Abstract

The studies aimed to assess a set of biomarkers for their correlations with disease activity/severity of patients with ankylosing spondylitis (AS). A total of 24 AS patients were treated with etanercept and prospectively followed for 12 weeks. Serum levels of TNF-α, IFN-γ, TGF-β, IL6, IL15, IL17, MMP3, and MICA were measured at baseline and after treatment. The change of these biomarkers was analyzed for correlations with MRI indices for joint inflammation, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, AS Disease Activity Score, serum CRP, and ESR. The Wilcoxon rank sum test was used to compare the biomarker levels between pre- and post-treatment and between pre-treatment and controls. Both step-wise procedures based on the Akaike information criterion (AIC) and least absolute shrinkage and selection operator with fivefold cross-validation were used to select the best model for pairwise correlations between the above clinical measures and the serum biomarkers. Serum levels of both MMP3 and IL6 were significantly higher in AS patients at baseline. After treatment, the levels of MMP3 decreased, but TGF-β and TNF-α increased significantly. The changes of serum MMP3 and MICA were significantly associated with MRI sacroiliac joint (SIJ) scores. CRP was positively correlated with serum MMP3 and IL6. The pattern of combined changes of serum MICA, MMP3, TGF-β, IL17, TNF-α, and IFN-γ predicted the MRI score of SIJ by logistic regression analysis. Specific serum biomarkers were significantly associated with clinical measures of AS. Most prominently, serum MMP3 level was found to have a positive correlation with the MRI score of SIJ and CRP. Serum MICA level negatively correlated with disease remission.

Nur mit Berechtigung zugänglich

Braun J, Bollow M, Remlinger G et al (1998) Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 41:58–67CrossRefPubMed

Bollow M, Fischer T, Reisshauer H, Backhaus M, Sieper J, Hamm B, Braun J (2000) Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis-cellularity correlates with the degree of enhancement detected by magnetic resonance imaging. Ann Rheum Dis 59:135–140CrossRefPubMedPubMedCentral

Appel H, Kuhne M, Spiekermann S et al (2006) Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow. Arthritis Rheum 54:1805–1813CrossRefPubMed

Appel H, Loddenkemper C, Grozdanovic Z et al (2006) Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis. Arthritis Res Ther 8:R143CrossRefPubMedPubMedCentral

Bennett AN, McGonagle D, O’Connor P et al (2008) Severity of baseline magnetic resonance imaging-evident sacroiliitis and HLA-B27 status in early inflammatory back pain predict radiographically evident ankylosing spondylitis at eight years. Arthritis Rheum 58:3413–3418CrossRefPubMed

Garrett S, Jenkinson T, Kennedy LG et al (1994) A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 21:2286–2291PubMed

Calin A, Garrett S, Whitelock H et al (1994) A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 21:2281–2285PubMed

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

Sveaas SH, Berg IJ, Provan SA et al (2015) Circulating levels of inflammatory cytokines and cytokine receptors in patients with ankylosing spondylitis: a cross-sectional comparative study. Scand J Rheumatol 44:118–124CrossRefPubMed

10.

Sieper J, Baraliakos X, Listing J et al (2005) Persistent reduction of spinal inflammation as assessed by magnetic resonance imaging in patients with ankylosing spondylitis after 2 yrs of treatment with the anti-tumour necrosis factor agent infliximab. Rheumatology 44:1525–1530CrossRefPubMed

11.

Puhakka KB, Jurik AG, Schiottz-Christensen B et al (2004) Magnetic resonance imaging of sacroiliitis in early seronegative spondyloarthropathy. Abnormalities correlated to clinical and laboratory findings. Rheumatology (Oxford) 43:234–237CrossRef

12.

Konca S, Keskin D, Cılız D, Bodur H, Sakman B (2012) Spinal inflammation by magnetic resonance imaging in patients with ankylosing spondylitis: association with disease activity and outcome parameters. Rheumatol Int 32:3765–3770CrossRefPubMed

13.

Gratacós J, Collado A, Filella X et al (1994) Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol 33:927–931CrossRefPubMed

14.

Ciccia F, Guggino G, Rizzo A et al (2015) Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis. Ann Rheum Dis 74:1739–1747CrossRefPubMed

15.

Yang C, Gu J, Rihl M et al (2004) Serum levels of matrix metalloproteinase 3 and macrophage colony-stimulating factor 1 correlate with disease activity in ankylosing spondylitis. Arthritis Rheum 51:691–699CrossRefPubMed

16.

Zhou X, Wang J, Zou H et al (2014) MICA, a gene contributing strong susceptibility to ankylosing spondylitis. Ann Rheum Dis 73:1552–1557CrossRefPubMed

17.

Hreggvidsdottir HS, Noordenbos T, Baeten DL (2014) Inflammatory pathways in spondyloarthritis. Mol Immunol 57:28–37CrossRefPubMed

18.

Braun J, Sieper J (2000) Anti-TNF alpha: a new dimension in the pharmacotherapy of the spondyloarthropathies. Ann Rheum Dis 59:404–407CrossRefPubMedPubMedCentral

19.

Papagoras C, Voulgari PV, Drosos AA (2015) Golimumab, the newest TNF-α blocker, comes of age. Clin Exp Rheumatol 33:570–577PubMed

20.

Callhoff J, Sieper J, Weiß A, Zink A, Listing J (2015) Efficacy of TNFα blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis. Ann Rheum Dis 74:1241–1248CrossRefPubMed

21.

Van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368CrossRefPubMed

22.

Maksymowych WP, Inman RD, Salonen D et al (2005) Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of sacroiliac joint inflammation in ankylosing spondylitis. Arthritis Rheum 53:703–709CrossRefPubMed

23.

Østergaard M, Maksymowych WP, Pedersen SJ, Chiowchanwisawakit P, Lambert RG (2009) Structural lesions detected by magnetic resonance imaging in the spine of patients with spondyloarthritis—definitions, assessment system, and reference image set. J Rheumatol Suppl 84:18–34.5CrossRef

24.

R Core Team (2015) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna URLhttps://www.R-project.org/

25.

Friedman J, Hastie T, Tibshirani R (2001) The elements of statistical learning. Vol. 1. Springer, Berlin Springer series in statistics

26.

Maksymowych WP, Lambert RG, Brown LS, Pangan AL (2012) Defining the minimally important change for the Spondylo Arthritis Research Consortium of Canada Spine and sacroiliac joint magnetic resonance imaging indices for ankylosing spondylitis. J Rheumatol 39:1666–1674CrossRefPubMed

27.

Maksymowych WP, Landewe R, Conner-Spady B et al (2007) Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis. Arthritis Rheum 56:1846–1853CrossRefPubMed

28.

Almodóvar R, Ríos V, Ocaña S et al (2014) Association of biomarkers of inflammation, cartilage and bone turnover with gender, disease activity, radiological damage and sacroiliitis by magnetic resonance imaging in patients with early spondyloarthritis. Clin Rheumatol 33:237–241CrossRefPubMed

29.

Spoorenberg A, van der Heijde D, de Klerk E et al (1999) Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis. J Rheumatol 26:980–984PubMed

30.

Chen C, Lin K, Yu D et al (2006) Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker of disease activity. Rheumatology 45:414–420CrossRefPubMed

31.

Maksymowych WP, Poole AR, Hiebert L et al (2005) Etanercept exerts beneficial effects on articular cartilage biomarkers of degradation and turnover in patients with ankylosing spondylitis. J Rheumatol 32:1911–1917PubMed

32.

Woo J, Lee H, Sung I et al (2007) Changes of clinical response and bone biochemical markers in patients with ankylosing spondylitis taking etanercept. Rheumatology 34:1753–1759

33.

Soliman E, Labib W, El Tantawi G et al (2012) Role of matrix metalloproteinase-3 (MMP-3) and magnetic resonance imaging of sacroiliitis in assessing disease activity in ankylosing spondylitis. Rheumatol Int 32:1711–1720CrossRefPubMed

34.

Xueyi L, Lina C, Zhenbiao W et al (2013) Levels of circulating Th17 cells and regulatory T cells in ankylosing spondylitis patients with an inadequate response to anti-TNF-α therapy. J Clin Immunol 33:151–161CrossRefPubMed

35.

François RJ, Neure L, Sieper J, Braun J (2006) Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases. Ann Rheum Dis 65:713–720CrossRefPubMed

36.

Schulz M, Dotzlaw H, Neeck G (2014) Ankylosing spondylitis and rheumatoid arthritis: serum levels of TNF-α and its soluble receptors during the course of therapy with etanercept and infliximab. Biomed Res Int 2014:675108CrossRefPubMedPubMedCentral

37.

Nadkarni S, Mauri C, Ehrenstein MR (2007) Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J Exp Med 204:33–39CrossRefPubMedPubMedCentral

38.

Groh V, Bahram S, Bauer S, Herman A, Beauchamp M, Spies T (1996) Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci U S A 93:12445–12450CrossRefPubMedPubMedCentral

39.

Zwirner NW, Dole K, Stastny P (1999) Differential surface expression of MICA by endothelial cells, fibroblasts, keratinocytes, and monocytes. Hum Immunol 60:323–330CrossRefPubMed

40.

Salih HR, Rammensee HG, Steinle A (2002) Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding. J Immunol 169:4098–4102CrossRefPubMed

41.

Kriegeskorte AK, Gebhardt FE, Porcellini S et al (2005) NKG2D-independent suppression of T cell proliferation by H60 and MICA. Proc Natl Acad Sci U S A 102:11805–11810CrossRefPubMedPubMedCentral

42.

Wang Q, Zhou X (2015) Associations of MICA polymorphisms with inflammatory rheumatic diseases. Open Rheumatol J 9:94–100CrossRefPubMedPubMedCentral

43.

Groh V, Rhinehart R, Randolph-Habecker J et al (2001) Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nat Immunol 2:255–260CrossRefPubMed

44.

Tieng V, Le Bouguenec C, du Merle L et al (2002) Binding of Escherichia coli adhesin AfaE to CD55 triggers cell-surface expression of the MHC class I-related molecule MICA. Proc Natl Acad Sci U S A 99:2977–2982CrossRefPubMedPubMedCentral

45.

Bahram S, Bresnahan M, Geraghty DE, Spies T (1994) A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci U S A 91:6259–6263CrossRefPubMedPubMedCentral

46.

Bauer S, Groh V, Wu J et al (1999) Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285:727–729CrossRefPubMed

47.

Groh V, Smythe K, Dai Z, Spies T (2006) Fas ligand-mediated paracrine T cell regulation by the receptor NKG2D in tumor immunity. Nat Immunol 7:755–762CrossRefPubMed

48.

Das H, Groh V, Kuijl C et al (2001) MICA engagement by human Vgamma 2Vdelta2 T cells enhances their antigen-dependent effector function. Immunity 15:83–93CrossRefPubMed

49.

Rincon-Orozco B, Kunzmann V, Wrobel P et al (2005) Activation of V gamma 9V delta 2 T cells by NKG2D. J Immunol 175:2144–2151CrossRefPubMed

50.

Andre P, Castriconi R, Espeli M et al (2004) Comparative analysis of human NK cell activation induced by NKG2D and natural cytotoxicity receptors. Eur J Immunol 34:961–971CrossRefPubMed

51.

Shi C, Li H, Couturier JP et al (2015) Allele specific expression of MICA variants in human fibroblasts suggests a pathogenic mechanism. Open Rheumatol J 9:60–64CrossRefPubMedPubMedCentral

Titel: Correlation of serum MMP3 and other biomarkers with clinical outcomes in patients with ankylosing spondylitis: a pilot study
verfasst von: Dongyi He
Qi Zhu
Quan Zhou
Qing Qi
Hongmei Sun
Liza M. Zachariah
Grace Wang
John D. Reveille
Yongtao Guan
Xiaodong Zhou
Publikationsdatum: 22.04.2017
Verlag: Springer London
Erschienen in: Clinical Rheumatology / Ausgabe 8/2017
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-017-3624-7

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

19.04.2024 | Vorhofflimmern | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Correlation of serum MMP3 and other biomarkers with clinical outcomes in patients with ankylosing spondylitis: a pilot study

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2017

Glucocorticoid-induced leucine zipper expression is associated with response to treatment and immunoregulation in systemic lupus erythematosus

Comparison of systemic lupus erythematosus (SLE) patients managed early after diagnosis in specialty versus community care clinics

Prominent midfoot involvement in children with enthesitis-related arthritis category of juvenile idiopathic arthritis

Hypomyopathic dermatomyositis associated with interstitial lung disease and good response to mycophenolate mofetil: case-based review

Evaluation of the effect of Elaeagnus angustifolia alone and combined with Boswellia thurifera compared with ibuprofen in patients with knee osteoarthritis: a randomized double-blind controlled clinical trial

Uric acid is independent cardiovascular risk factor, as manifested by increased carotid intima-media thickness in rheumatoid arthritis patients

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Update Innere Medizin