#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
CS
proLékaře.cz / Journals / Clinical Biochemistry and Metabolism / 2021 - 1

Overview of biomarkers of synovial fluid in joint diseases

Czech version

Authors: I. Bystroňová 1,2;  P. Kušnierová 2,3;  P. Walder 6;  R. Hlubek 6;  J. Rolová 4,5;  D. Stejskal 2,3
Authors‘ workplace: Ústav epidemiologie a ochrany veřejného zdraví, Lékařská fakulta, Ostravská univerzita 1;  Ústav laboratorní medicíny, Oddělení klinické biochemie, Fakultní nemocnice Ostrava 2;  Katedra biomedicínských oborů, Lékařská fakulta, Ostravská univerzita 3;  Katedra interních oborů, Lékařská fakulta, Ostravská univerzita 4;  Interní klinika, Revmatologická ambulance, Fakultní nemocnice Ostrava 5;  Oddělení ortopedické, Fakultní nemocnice Ostrava 6
Published in: Klin. Biochem. Metab., 29, 2021, No. 1, p. 11-18

Overview

Objective: Presentation of current knowledge of biochemical markers of synovial fluid (BF) in joint diseases.

Design: literature review

Settings: Institute of Laboratory Medicine, Department of Clinical Biochemistry, University Hospital Ostrava

Material and Methods: Based on the study of the literature, the basic biochemical markers of synovial fluid (glucose, GLU; total protein, TP; lactate, LAC; lactate dehydrogenase, LDH; energy balance coefficient, CEB; uric acid, UA; cholesterol, CHOL), inflammatory biomarkers of synovial fluid (C-reactive protein, CRP; procalcitonin, PCT; presepsin, PRES; interleukin-6, IL-6) and new research biomarkers of synovial fluid (interleukin-1 beta, IL-1β; alpha-defensins or human neutrophil peptides 1-3, HNP1-3; cartilage oligomeric matrix protein, COMP; calprotectin, lactoferrin, matrix metalloproteinases 1 and 3, MMP-1, MMP-3; neutrophil gelatinase-associated lipocalin, NGAL and polymorphonuclear elastase, PMNE) are described in a clear work . Their characteristics, uses and connections with joint infections are described, as well as the results of some studies.

Results: According to 39 selected publications from 1962 to 2021, it was treated that all of these biomarkers have their application in joint diseases and exist by determining not only in the blood but also in the synovial fluid. The level of glucose in ST is reduced in joint infections by up to 1.11-5.56 mmol.L-1 compared to serum, determination of lactate is especially important in septic arthritis and the energy balance coefficient serves to determine the nature and intensity of the inflammatory response and is calculated just from the ratio of glucose to lactate. For periprosthetic joint infections (PJIs), the cut-off value for GLU in ST is 2.4 mmol.L-1, AUC (area under the curve) 0.829; sensitivity 79.2 %, specificity 78.6 % and for LAC in ST the cut-off value is 8.3 mmol.L-1, AUC (area under the curve) 0.844; sensitivity 71.4 % and specificity 88.0 %. Elevated levels of total protein and LDH in ST occur in arthritis and gout. For PJI, the cut-off value for LDH in ST is 1423 U.L-1, the AUC (area under the curve) 0.779; sensitivity 84.0 % and specificity 62.1 %. The presence of uric acid in ST is important especially for the diagnosis of gout and elevated cholesterol levels in ST for the diagnosis of rheumatoid arthritis. Cut-off value of KM in serum is 369 μmol.L-1, cut-off value of KM in ST 393 μmol.L-1 and cut‑off value of synovial fluid to serum ratio 1.01. CRP in ST (cut-off value 2.8‑12.2 mg.L-1, sensitivity 92.0 %, specificity 90.0 %), IL-6 in ST (cut-off value 9000 ng.L-1, sensitivity 46.9 %, specificity 97.6 % or cut-off value 30.750 ng.L-1, sensitivity 90.9 %, specificity 94.7 %) and NGAL in ST (cut-off value 152 µg.L-1, sensitivity 86-95 %, specificity 77-95 %) are considered suitable biomarkers of PJIs, whereas PCT (cut-off value about 0.5 µg.L-1) due to its low sensitivity (53.0 %) is not suitable for this purpose. Presepsin in ST is suitable not only for the diagnosis of PJI, but also for septic arthritis. The cut-off value of PRES in ST in patients with septic arthritis is 1262 ng.L-1, sensitivity 85.7 % and specificity 85.2 %. IL-1β levels in ST in patients without rheumatic disease or joint effusion are not detectable, in rheumatoid arthritis or osteoarthritis they increase, ranging from tens to hundreds of ng.L-1. The cut-off of alpha-defensin in ST when comparing the results of patients with infectious arthritis compared to aseptic patients with osteoarthritis was set at 62.5 mg.L-1 and the “grey zone” was set at 63-108 mg.L-1 for patients with non-infectious reactive arthritis and rheumatoid arthritis. Several studies have shown that cartilage matrix degradation during degenerative joint disease and proteins such as COMP, MMP-1 and MMP-3 are released into the synovial fluid. The highest concentrations of total COMP, MMP‑1 and MMP-3 were found in patients with osteoarthritis. Calprotectin or PMNE levels can be a valuable tool in the diagnosis of rheumatic disease. The cut-off value of calprotectin for distinguishing septic arthritis from non-septic inflammatory arthritis is 150 mg.L-1 with a sensitivity of 76.0 % and a specificity of 94.0 % and the cut-off value of calprotectin for PJI is 173 mg.L-1 with a sensitivity of 95.2 % and specificity 97.6 %. Determination of lactoferrin in rheumatoid joint or septic arthritis could also be of clinical importance..

Conclusion: Determination of biomarkers in synovial fluid should become part of the routine determination of joint diseases. Whether one test or a panel of tests will help us to determine whether synovial fluid is of infectious origin or not, especially in cases where the etiology is unclear, the disease is modified by already applied antibiotics or previous surgical procedures, and the causative agent is not proven. In these cases, diagnosis is not easy, but it must still be as fast, highly sensitive and specific as possible.

Keywords: synovial fluid, biomarkers, joint diseases, joint infections.

Keywords:

Synovial fluid – biomarkers – joint diseases – joint infections

Sources
  1. Gatter, R. A., Schymacher, H. R. A Practical Handbook of Joint Fluid Analysis. 2nd Ed. Philadelphia: Lea & Febiger, 1991, 122 s.
  2. McBride, L. J. Textbook of Urinalysis and Body Fluids: A Clinical Approach. Philadelphia: Lippincott, 1998, 286 s.
  3. Lenski, M., Scherer, M. A. Synovial IL-6 as inflammatory marker in periprosthetic joint infections. J. Arthroplasty, 2014, 29(6), s. 1105-1109.
  4. Ross, D. L., Neeley, A. E. Textbook of Urinalysis and Body Fluids. New York: Appleton-Century-Crofts, 1983, 336 s., ISBN 978-0838589137
  5. Kelbich, P., Hejčl, A., Selke-Krulichová, I., Procházka, J., Hanuljaková, E. et al. Coefficient of energy balance, a new parameter for basic investigation of the cerebrospinal fluid. Clin. Chem. Lab. Med., 2014, 52, s.1009-1017.
  6. Kelbich, P., Hejčl, A., Procházka, J., Hanuljaková, E., Staněk, I. et al. Cytological-energetic examination of the extra-vascular body fluids, including the cerebrospinal fluid. Biochem. Anal. Biochem., 2016, 5, s. 4.
  7. Kjeldsberg, C. R., Knight, J. A. Body Fluids: Laboratory Examination of Amniotic, Cerebrospinal, Seminal, Serous & Synovial Fluids, A Textbook Atlas. Chicago, IL: ASCP Press, 1993, 436 s., ISBN 978-0891893448
  8. Vaidya, B., Bhochhibhoya, M., Nakarmi, S. Synovial fluid uric acid level aids diagnosis of gout. Biomed. Reports, 2018, 9, s. 60-64.
  9. Bole, G. G. Synovial Fluid Lipids in Normal Indivi-duals and Patients with Rheumatoid Arthritis. Arthritis and Rheumatism, 1962, 5(6), s. 589-601.
  10. Wang, C., Wang, Q., Li, R., Duan, J.-Y., Wang, C.-B. Synovial Fluid C-reactive Protein as a Diagnostic Marker for Periprosthetic Joint Infection: A Systematic Review and Meta-analysis. Chin. Med. J. (Engl.), 2016, 129(16), s. 1987-1993.
  11. Tetreault, M. W., Wetters, N. G., Gross, C. E., Della Valle, C. J. Is Synovial C-reactive Protein a Useful Marker for Periprosthetic Joint Infection? Clin. Orthop. Relat. Res., 2014, 472, s. 3997-4003.
  12. Parvizi, J., Jacovides, C., Adeli, B., Jung, K. A., Hozack, W. J., Mark, B. Coventry Award: syno-vial C-reactive protein: a prospective evaluation of a molecular marker for periprosthetic knee joint infection. Clin. Orthop. Relat. Res., 2012, 470, s. 54–60.
  13. Saeed, K., Dryden, M., Sitjar, A., White, G. Measuring synovial fluid procalcitonin levels in distinguishing cases of septic arthritis, including prosthetic joints, from other causes of arthritis and aseptic loosening. Infection, 2013, 41, s. 845-849.
  14. Wang, C., Zhong, D., Liao, Q., Kong, L., Liu, A. and Xiao, H. Procalcitonin levels in fresh serum and fresh synovial fluid for the differential diagnosis of knee septic arthritis from rheumatoid arthritis, osteoarthritis and gouty arthritis. Exp. Therapeut. Med., 2014, 8, s. 1075-1080.
  15. Xie, K., Qu, X., Yan, M. Procalcitonin and α-defensin for diagnosis of periprosthetic joint infections. J. Arthroplasty, 2017, 32, s. 1387-1394.
  16. Imagama, T., Tokushige, A., Seki, K., Seki, T., Nakashima, D., Ogasa, H., Sakai, T., Taguchi, T. Early diagnosis of septic arthritis using syno-vial fluid  presepsin: A preliminary study. J. Infect. Chemother., 2019, 25(3), s. 170-174.
  17. Marazzi, M. G., Randelli, F., Brioschi, M. et al. Presepsin: A potential biomarker of PJI? A comparative analysis with known and new infection biomarkers. Int. J. Immunopathol. Pharmacol., 2018, 31, ID 394632017749356.
  18. Imagama, T., Seki, K., Seki, T., Tokushige, A., Matsuki, Y., Yamazaki, K., Nakashima, D., Okazaki, T., Hirata, K., Yamamoto, M., Tanaka, H., Sakai, T. Synovial fluid presepsin as a no-vel biomarker for the rapid differential diagnosis of native joint septic arthritis from crystal arthritis. Interna. J Inf. Dis., 2021, 102, s. 472-477.
  19. Berbari, E., Mabry, T., Tsaras, G. et al. Inflammatory blood laboratory levels as markers of prosthetic joint infection: a systematic review and meta-analysis. J. Bone Joint Surg., 2010, 92-A, s. 2102-2109.
  20. Randau, T. M., Friedrich, M. J., Wimmer, M. D. et al. Interleukin-6 in Serum and in Synovial Fluid Enhances the Differentiation between Periprosthetic Joint Infection and Aseptic Loosening.  PloS One, 2014, 9(2), e89045, s. 1-6.
  21. McNulty, A. M., Rothfusz, N. E., Leddy, H. A., Guilak, F. Synovial Fluid Concentrations and Relative Potency of Interleukin-1 Alpha and Beta in Cartilage and Meniscus Degradation. J Orthopaed. Res., 2013, 31(7), s. 1039-1045.
  22. Deirmengian C., Hallab N., Tarabishz A., Valle C. D., Jacobs J. J., Lonner, J., Booth, R. E. Synovial Fluid Biomarkers for Periprosthetic Infection. Clin. Orthop. Relat. Res., 2010, 468, s. 2017-2023.
  23. Dinarello, C. A. The interleukin-1 family: 10 years of discovery. FASEB J., 1994, 8, s. 1314–1325.
  24. Melicherčík, P., Klapková, E., Kotaška, K., Jahoda, D., Landor, I., Čeřovský, V. High-performance liquid chromatography as a novel method for the determination of α-Defensins in synovial fluid for diagnosis of orthopedic infections. Diagnostics (Basel), 2020, 10(1), s. 33.
  25. Dungl, P. et al. Orthopedie, Grada Publishing, a.s. 2014, 1192 s. ISBN 978-80-247-4357-8.
  26. Human HNP1-3 ELISA Kit, Product information and manual, HycultBiotech, Edition 08-16. [online] [cit. 2020-10-06]. Dostupný na www: https://www.hycultbiotech.com/hk317-01.].
  27. Lorenzo P., Aspberg A., Saxne T., Önnerfjord P. Quantification of cartilage oligomeric matrix protein (COMP) and a COMP neoepitope in synovial fluid of patients with different joint disorders by novel automated assays. Osteoarthritis Cartilage, 2017, 25(9), s. 1436-1442.
  28. DiCesare, P., Hauser, N., Lehman, D., Pasumarti, S., Paulsson, M. Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon. FEBS Lett., 1994, 354, s. 237-240.
  29. Ometto F., Friso L., Astorri D., Botsios C., Raffeiner B., Punzi L., Doria A. Calprotectin in rheumatic diseases. Exp. Biol. Med., 2017, 242, s. 859-873.
  30. Baillet, A., Trocmé, C., Romand, X., Nguyen, C. M. V., Courtier, A., Toussaint, B., Gaudin, P., Epaulard, O. Calprotectin discriminates septic arthritis from pseudogout and rheumatoid arthritis. Rheumatology, 2019, 58, s. 1644-1648.
  31. Zhang, Z., Cai, Y., Zhang, C., Li, W., Yang, B., Zhang, W. The value of calprotectin in synovial fluid for the diagnosis of chronic prosthetic joint infection. Bone Joint. Res., 2020, 9(8), s. 450-457.
  32. Wong S. H., Francis N., Chahal H., Raza K., Salmon M., Scheel/Toellner D., Lord J. M. Lactoferrin is a survival factor for neutrophils in rheumatoid synovial fluid. Rheumatology, 2009, 48, s. 39-44.
  33. Guillen, C., McInnes, I. B., Kruger, H., Brock, J. H. Iron, lactoferrin and iron regulatory protein acti-vity in the synovium; relative importance of iron loading and the inflammatory response. Ann. Rheum. Dis., 1998, 57, s. 309–314.
  34. Li, H., Li, L., Min, J., Yang, H., Xu, X., Yuan, Y., Wang, D. Levels of metalloproteinase (MMP-3, MMP-9), NF-kappab ligand (RANKL), and nitric oxide (NO) in peripheral blood of osteoarthritis (OA) patients. Clin. Lab., 2012, 58, s. 755–762.
  35. Nguyen, L. T., Sharma, A. R., Chakraborty, C., Saibaba, B., Ahn, M.-E., Lee, S.-S. Review of Prospects of Biological Fluid Biomarkers in Ostaoarthritis. Int. J. Mol. Sci., 2017, 18, s. 601.
  36. Dijkman, C., Thomas, A. R., Koenraadt, K. L. M., Ermens, A. A. M., van Geenen R. C. I. Sy-novial neutrophilic gelatinase-associated lipocalin in the diagnosis of periprosthetic joint infection after total knee arthroplasty. Arch.Orthop. Trauma Surg., 2020, 140(7), s. 941-947.
  37. Vergara, A., Fernández-Pittol, M. J., Munoz-Mahamud, E., Morata L., Bosch, J., Vila, J., Soriano, A., Casals-Pascual, C. Evaluation of Lipocalin-2 as a Biomarker of Periprosthetic Joint Infection. J. Arthroplasty, 2019, 34(1), s. 123-125.
  38. Huang, H., Ideh, R. C., Gitau, E., Thézénas, M. L., Jallow, M., Ebruke, B., Chimah, O., Oluwalana, C., Karanja, H., Mackenzie, G., Adegbola, R. A., Kwiatkowski, D., Kessler, B. M., Berkley, J. A., Howiq, S. R., Casals-Pascual, C. Discovery and validation of biomarkers to guide clinical management of pneumonia in African cildren. Clin. Infect.Dis., 2014, 58(12), s. 1707-1715.
  39. Momohara, S., Kashiwazaki, S., Inoue, K., Saito, S., Nakagawa, T. Elastasa from polymorphonuclear leukocyte in articular cartlage and synovil fluids of patients with rheumatoid arthritis. Clin. Rheumatol., 1997, 16, s. 133-139.
Labels
Clinical biochemistry Nuclear medicine Nutritive therapist
EDITORIAL
Quantitative determination of hemoglobin in stool - preanalytical and analytical aspects
Measurement of anti-SARS-CoV-2 antibodies nucleocapsid versus spike, ECLIA versus ELISA
Analytes of clinical biochemistry and hematology in COVID-19
Doporučený diagnostický a léčebný postup pro všeobecné praktické lékaře: POCT metody v ordinaci praktického lékaře
Doporučení České společnosti klinické biochemie ČLS JEP k využití nádorových markerů v klinické praxi
Article was published in

Clinical Biochemistry and Metabolism

Issue 1
2021 Issue 1
Most read in this issue
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#