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Interleukin 18, soluble cluster of differentiation 40, platelet factor 4 variant 1, and neutrophil gelatinase-associated lipocalin can be used as biomarkers to aid activity and diagnosis in ocular Behçet’s disease

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Abstract

Purpose

The molecules human interleukin (IL-18), the soluble cluster of differentiation (sCD40), platelet factor 4 variant 1 (PF4V1), and neutrophil gelatinase-associated lipocalin (NGAL) are all markers of inflammation in biological systems and are linked to prognosis in several inflammatory diseases as well. Since there is no study in which the above-mentioned molecules are studied together in ocular Behçet's disease (OBD), the aim of this study is to reveal whether these molecules are activity markers in active (OABD) and inactive (OIBD) disease.

Methods

30 OABD and 30 OIBD and 30 healthy individuals were included in the study. IL-18, sCD40, PF4V1, and NGAL molecules were studied in blood samples by the ELISA method.

Results

When OABD and OIBD were compared to healthy individuals, the levels of IL-18, sCD40, PF4V1, and NGAL molecules were found to be statistically significant. These values were even more significantly higher in patients with OABD.

Conclusion

When ROC values of IL-18, sCD40, PF4V1, and NGAL are evaluated, it is clear that these four molecules can be used as biomarkers to aid activity and diagnosis in OBD.

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References

  1. Behçet H (1937) Über rezidivierende, aphtöse, durch ein Virus verursachte Geschwüre am Mund, am Auge und an den Genitalien. Dermatol Wochenschr 105:1152–1163

    Google Scholar 

  2. Turgut YB, Turgut M (2020) Turkish scientist Hulusi Behçet (1889–1948) and his contribution to the medical world. Childs Nerv Syst 36:665–666. https://doi.org/10.1007/s00381-019-04081-8

    Article  PubMed  Google Scholar 

  3. Tan SY, Poole PS (2016) Hulusi Behçet (1889–1948): passion for dermatology. Singap Med J 57:408–409. https://doi.org/10.11622/smedj.2016123

    Article  Google Scholar 

  4. Bansal R, Gupta V, Gupta A (2010) Current approach in the diagnosis and management of panuveitis. Indian J Ophthalmol 58:45–54. https://doi.org/10.4103/0301-4738.58471

    Article  PubMed  PubMed Central  Google Scholar 

  5. Emmi G, Silvestri E, Squatrito D et al (2014) Emmi L. Behçet’s syndrome pathophysiology and potential therapeutic targets. Intern Emerg Med 9:257–265. https://doi.org/10.1007/s11739-013-1036-5

    Article  PubMed  Google Scholar 

  6. Tong B, Liu X, **ao J et al (2019) Immunopathogenesis of Behcet’s disease. Front Immunol 10:665. https://doi.org/10.3389/fimmu.2019.00665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Balbaba M, Ulaş F, Postacı SA et al (2020) Serum cortistatin levels in patients with ocular active and ocular inactive Behçet disease. Ocul Immunol Inflamm 28:601–605. https://doi.org/10.1080/09273948.2019.1610461

    Article  CAS  PubMed  Google Scholar 

  8. Kany S, Vollrath JT, Relja B (2019) Cytokines in inflammatory disease. Int J Mol Sci 20:6008. https://doi.org/10.3390/ijms20236008

    Article  CAS  PubMed Central  Google Scholar 

  9. Cronkite DA, Strutt TM (2018) The regulation of inflammation by innate and adaptive lymphocytes. J Immunol Res 2018:1467538. https://doi.org/10.1155/2018/1467538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Musabak U, Pay S, Erdem H et al (2006) Serum interleukin-18 levels in patients with Behçet’s disease. is its expression associated with disease activity or clinical presentations? Rheumatol Int 26:545–550. https://doi.org/10.1007/s00296-005-0029-8

    Article  CAS  PubMed  Google Scholar 

  11. Oztas MO, Onder M, Gurer MA et al (2005) Serum interleukin 18 and tumour necrosis factor-alpha levels are increased in Behcet’s disease. Clin Exp Dermatol 30:61–63. https://doi.org/10.1111/j.1365-2230.2004.01684.x

    Article  CAS  PubMed  Google Scholar 

  12. Kawabe T, Matsushima M, Hashimoto N et al (2011) CD40/CD40 ligand interactions in immune responses and pulmonary immunity. Nagoya J Med Sci 73:69–78

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Elgueta R, Benson MJ, de Vries VC et al (2009) Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev 229:152–172. https://doi.org/10.1111/j.1600-065X.2009.00782.x

    Article  CAS  PubMed  Google Scholar 

  14. Linke B, Schreiber Y, Picard-Willems B et al (2017) Activated platelets induce an anti-inflammatory response of monocytes/macrophages through cross-regulation of PGE2 and cytokines. Mediat Inflamm 2017:1463216. https://doi.org/10.1155/2017/1463216

    Article  CAS  Google Scholar 

  15. Raziuddin S, Al-Dalaan A, Bahabri S et al (1998) Divergent cytokine production profile in Behçet’s disease. Altered Th1/Th2 cell cytokine pattern. J Rheumatol 25:329–333

    CAS  PubMed  Google Scholar 

  16. Fleischer J, Grage-Griebenow E, Kasper B et al (2002) Platelet factor 4 inhibits proliferation and cytokine release of activated human T cells. J Immunol 169:770–777. https://doi.org/10.4049/jimmunol.169.2.770

    Article  CAS  PubMed  Google Scholar 

  17. Joglekar M, Khandelwal S, Cines DB et al (2015) Heparin enhances uptake of platelet factor 4/heparin complexes by monocytes and macrophages. J Thromb Haemost 13:1416–1427. https://doi.org/10.1111/jth.13003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kaiko GE, Horvat JC, Beagley KW et al (2008) Immunological decision-making: how does the immune system decide to mount a helper T-cell response? Immunology 123:326–338. https://doi.org/10.1111/j.1365-2567.2007.02719.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Perazzio SF, Soeiro-Pereira PV, Dos Santos VC et al (2017) Soluble CD40L is associated with increased oxidative burst and neutrophil extracellular trap release in Behçet’s disease. Arthritis Res Ther 19:235. https://doi.org/10.1186/s13075-017-1443-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schmitz-Huebner U, Knop J (1984) Evidence for an endothelial cell dysfunction in association with Behçet’s disease. Thromb Res 34:277–285. https://doi.org/10.1016/0049-3848(84)90384-0

    Article  CAS  PubMed  Google Scholar 

  21. Abella V, Scotece M, Conde J et al (2015) The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases. Biomarkers 20:565–571. https://doi.org/10.3109/1354750X.2015.1123354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Passov A, Petäjä L, Pihlajoki M et al (2019) The origin of plasma neutrophil gelatinase-associated lipocalin in cardiac surgery. BMC Nephrol 20:182. https://doi.org/10.1186/s12882-019-1380-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Clifton MC, Rupert PB, Hoette TM et al (2019) Parsing the functional specificity of Siderocalin/Lipocalin 2/NGAL for siderophores and related small-molecule ligands. J Struct Biol X 2:100008. https://doi.org/10.1016/j.yjsbx.2019.100008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Salom D, Sanz-Marco E, Mullor JL et al (2010) Aqueous humor neutrophil gelatinase-associated lipocalin levels in patients with idiopathic acute anterior uveitis. Mol Vis 16:1448–1452

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Li T, Yu L, Wen J et al (2016) An early-screening biomarker of endometrial carcinoma: NGAL is associated with epithelio-mesenchymal transition. Oncotarget 7(52):86064–86074. https://doi.org/10.18632/oncotarget.13340

    Article  PubMed  PubMed Central  Google Scholar 

  26. Thorsvik S, Damås JK, Granlund AV et al (2017) Fecal neutrophil gelatinase-associated lipocalin as a biomarker for inflammatory bowel disease. J Gastroenterol Hepatol 32:128–135. https://doi.org/10.1111/jgh.13598

    Article  CAS  PubMed  Google Scholar 

  27. Suzuki M, Wiers KM, Klein-Gitelman MS et al (2008) Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis. Pediatr Nephrol 23:403–412. https://doi.org/10.1007/s00467-007-0685-x

    Article  PubMed  Google Scholar 

  28. Shang W, Wang Z (2017) The update of NGAL in acute kidney injury. Curr Protein Pept Sci 18:1211–1217. https://doi.org/10.2174/1389203717666160909125004

    Article  CAS  PubMed  Google Scholar 

  29. Damman K, Valente MAE, van Veldhuisen DJ et al (2017) Plasma neutrophil gelatinase-associated lipocalin and predicting clinically relevant worsening renal function in acute heart failure. Int J Mol Sci 18:1470. https://doi.org/10.3390/ijms18071470

    Article  CAS  PubMed Central  Google Scholar 

  30. Ding L, Hanawa H, Ota Y et al (2010) Lipocalin-2/neutrophil gelatinase-B associated lipocalin is strongly induced in hearts of rats with autoimmune myocarditis and in human myocarditis. Circ J 74:523–530. https://doi.org/10.1253/circj.cj-09-0485

    Article  CAS  PubMed  Google Scholar 

  31. Woo HJ, Min JK, Bai CH et al (2008) Expression of neutrophil gelatinase-associated lipocalin in nasal polyps. Arch Otolaryngol Head Neck Surg 134:1182–1186. https://doi.org/10.1001/archotol.134.11.1182

    Article  PubMed  Google Scholar 

  32. Artunc-Ulkumen B, Guvenc Y, Goker A et al (2015) Relationship of neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin levels with the presence and severity of the preeclampsia. J Matern Fetal Neonatal Med 28:1895–1900. https://doi.org/10.3109/14767058.2014.972926

    Article  CAS  PubMed  Google Scholar 

  33. Katano M, Okamoto K, Arito M et al (2009) Implication of granulocyte-macrophage colony-stimulating factor induced neutrophil gelatinase-associated lipocalin in pathogenesis of rheumatoid arthritis revealed by proteome analysis. Arthritis Res Ther 11:R3. https://doi.org/10.1186/ar2587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Siddappa PK, Kochhar R, Sarotra P et al (2018) Neutrophil gelatinase-associated lipocalin: an early biomarker for predicting acute kidney injury and severity in patients with acute pancreatitis. JGH Open 3:105–110. https://doi.org/10.1002/jgh3.12112

    Article  PubMed  PubMed Central  Google Scholar 

  35. Uzkeser H, Karatay S, Yildirim K et al (2011) Antistreptolysin O levels in patients with Behcet’s disease. Eurasian J Med 43:169–172. https://doi.org/10.5152/eajm.2011.33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Balbaba M, Ulaş F, Yıldırım H et al (2020) Thiol/disulfide homeostasis in patients with ocular-active and ocular-inactive Behçet disease. Int Ophthalmol 40:2643–2650. https://doi.org/10.1007/s10792-020-01445-x

    Article  PubMed  Google Scholar 

  37. Tanaka R, Murata H, Takamoto M et al (2016) Behçet’s disease ocular attack score 24 and visual outcome in patients with Behçet’s disease. Br J Ophthalmol 100:990–994. https://doi.org/10.1136/bjophthalmol-2015-307362

    Article  PubMed  Google Scholar 

  38. Kaburaki T, Namba K, Sonoda KH et al (2014) Ocular Behçet disease research group of Japan. Behçet’s disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab. Jpn J Ophthalmol 58:120–130

    Article  CAS  Google Scholar 

  39. International Study Group for Behçet’s Disease (1990) Criteria for diagnosis of Behçet’s disease. Lancet 335:1078–1080. https://doi.org/10.1016/0140-6736(90)92643-V

    Article  Google Scholar 

  40. Bhakta BB, Brennan P, James TE, Chamberlain MA, Noble BA, Silman AJ (1999) Behçet’s disease: evaluation of a new instrument to measure clinical activity. Rheumatology (Oxford) 38(8):728–733. https://doi.org/10.1093/rheumatology/38.8.728

    Article  CAS  Google Scholar 

  41. Zhou ZY, Chen SL, Shen N et al (2012) Cytokines and Behcet’s disease. Autoimmun Rev 11:699–704. https://doi.org/10.1016/j.autrev.2011.12.005

    Article  CAS  PubMed  Google Scholar 

  42. Park UC, Kim TW, Yu HG (2014) Immunopathogenesis of ocular Behçet’s disease. J Immunol Res 2014:653539. https://doi.org/10.1155/2014/653539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hamzaoui K, Hamzaoui A, Guemira F et al (2002) Cytokine profile in Behçet’s disease patients. Relationship with disease activity. Scand J Rheumatol 31:205–210. https://doi.org/10.1080/030097402320318387

    Article  PubMed  Google Scholar 

  44. Yasuda K, Nakanishi K, Tsutsui H (2019) Interleukin-18 in health and disease. Int J Mol Sci 20:649. https://doi.org/10.3390/ijms20030649

    Article  CAS  PubMed Central  Google Scholar 

  45. Cardone J, Le Friec G, Kemper C (2011) CD46 in innate and adaptive immunity: an update. Clin Exp Immunol 164:301–311. https://doi.org/10.1111/j.1365-2249.2011.04400.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kral JB, Schrottmaier WC, Salzmann M et al (2016) Platelet interaction with innate immune cells. Transfus Med Hemother 43:78–88. https://doi.org/10.1159/000444807

    Article  PubMed  PubMed Central  Google Scholar 

  47. Arango Duque G, Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5:491. https://doi.org/10.3389/fimmu.2014.00491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tanaka T, Narazaki M, Kishimoto T (2014) IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 6:a016295. https://doi.org/10.1101/cshperspect.a016295

    Article  PubMed  PubMed Central  Google Scholar 

  49. Rosales C (2018) Neutrophil: a cell with many roles in inflammation or several cell types? Front Physiol 9:113. https://doi.org/10.3389/fphys.2018.00113

    Article  PubMed  PubMed Central  Google Scholar 

  50. Chakraborty S, Kaur S, Guha S et al (2012) The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim Biophys Acta 1826:129–169. https://doi.org/10.1016/j.bbcan.2012.03.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Donmez N (2012) Lipocalin 2 levels in patients with Behçet's disease, Kahraman Maras Sutcu İmam University, specialization thesis, Kahramanmaras, Turkey

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Funding

No financial support was received for this study.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Elazig Fethi Sekin City Hospital, Health Science University, Elazig Campus, Elazig, Turkey

    Fatih Celik, Fatih Cem Gul & Sabiha Gungor Kobat

  2. Health Services Vocational School, Ahi Evran University, Kirsehir, Turkey

    Ebru Coteli

  3. Department of Ophthalmology, Haseki Education Research Hospital, Istanbul, Turkey

    Ercan Ozsoy

  4. Department of Internal Medicine (Endocrine and Metabolism Disease), Elazig Fethi Sekin City Hospital, Health Science University, Elazig Campus, Elazig, Turkey

    Zuhal Karaca Karagoz

  5. Department of Cardiovascular Surgery, Elazig Fethi Sekin City Hospital, Health Science University, Elazig Campus, Elazig, Turkey

    Suna Aydin

  6. Department of Anatomy, Medical School, Firat University, Elazig, Turkey

    Suna Aydin & Ramazan Fazil Akkoc

  7. Department of Internal Medicine (Endocrine and Metabolism Disease), Medical School, Firat University, Elazig, Turkey

    Kader Ugur

  8. Department of Medical Biochemistry, Yerköy State Hospital, Yozgat, Turkey

    Meltem Yardim

  9. Department of Medical Biology, Medical School, Erzincan Binali Yildirim University, Erzincan, Turkey

    İbrahim Sahin

  10. Department of Medical Biochemistry and Clinical Biochemistry, (Firat Hormones Research Group), Medical School, Firat University, Elazig, Turkey

    İbrahim Sahin & Suleyman Aydin

  11. Department of Histology and Embryology, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey

    Mehmet Hanifi Yalcin

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  1. Fatih Celik
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  3. Fatih Cem Gul
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Contributions

FC, SA, EC, EO, FCG, ZKK, Suna A contributed to concept, design, intellectual content and drafted the article. İS contributed to design, concept, and statistical analysis. FC, FCG, Suna A, SGK, EO, MY, RFA, MHY acquired data and interpreted data. The whole authors contributed to data analysis and intellectual content. FC acquired data, drafted the article and interpreted data. The whole authors contributed to data analysis.

Corresponding author

Correspondence to Suleyman Aydin.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of Fırat University Faculty of Medicine ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Celik, F., Coteli, E., Gul, F.C. et al. Interleukin 18, soluble cluster of differentiation 40, platelet factor 4 variant 1, and neutrophil gelatinase-associated lipocalin can be used as biomarkers to aid activity and diagnosis in ocular Behçet’s disease. Int Ophthalmol 42, 3321–3331 (2022). https://doi.org/10.1007/s10792-022-02331-4

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