Differential Biochemical Markers Identified in Inflammatory Processed Synovial Fluid

Joint infections with a non-specific presentation are difficult to diagnose, mainly due to the absence of specific clinical signs and symptoms, relative lack of accurate laboratory tests, low virulence due to previous treatment, and biofilm ability of the pathogens.

This difficulty is especially true for patients treated with non-targeted antibiotics, including patients with implanted joint replacements. New biochemical markers are being sought to help quickly determine the extent of the inflammatory process taking place in the joint cavity in routine biochemical practice, either due to its increased concentration in synovial fluid (SF) or directly in serum/plasma.


Clinical Biochemists and their colleagues at the University of Ostrava (Ostrava, Czech Republic) sought to identify biochemical markers in Synovial Fluid (SF) that can predict susceptibility to ongoing inflammatory processes in the joint cavity. Ninety-two consecutive patients were divided into four SF groups based on clustering analysis: non-inflammatory SF (73%), inflammatory-non-pyogenic (12%), inflammatory-pyogenic (10%), or hemorrhagic (5%).

The team measured and compared the levels of the following biochemical markers in SF: glucose, lactate, total protein, uric acid, C-Reactive Protein (CRP), Leukocyte Count (WBC), Mononuclear (MNP), Polymorphonuclear (PMN), Interleukin (IL)-1 beta, IL6, Procalcitonin, Presepsin, Neutrophil Gelatinase-Associated Lipocalin (NGAL), Human Neutrophil Defensin 1-3 (HNP1-3), Cartilage Oligomeric Matrix Protein, Lactoferrin (HLF2), Polymorphonuclear Elastase (PMNE), Matrix Metalloproteinase (MMP)-1, and MMP-3. The concentrations of the biochemical biomarkers were determined on an AU 5800 automated analyzer (Beckman Coulter, Brea, CA, USA). They analyzed hematological parameters, relative and absolute numbers of leukocytes (WBC), and (MNP) and PMN leukocyte counts on a XN-9000 Automated in Body Fluid mode (Sysmex, Kobe, Japan).

The scientists reported that a significant difference between WBC, PMN, MNP, CRP, IL-1β, IL-6, HNP1-3, HLF2, PMNE, and individual groups of SF type. They also found a significant correlation between WBC and PMN, MNP, and CRP; PMN and HNP1-3 and PMNE; IL-6 and PMNE; IL-1β and NGAL, HLF2, and PMNE; HNP1-3 and NGAL, HLF2, and PMNE; NGAL and HLF2 and PMNE; and HLF2 and PMNE concentrations in all SF groups, between WBC and MNP; IL-1β and NGAL and MMP-3; HNP1-3 and PMNE; and NGAL and HLF2 concentrations in the non-inflammatory SF group, and between PMN and MNP in the inflammatory-non-pyogenic and inflammatory-pyogenic SF groups. PMN, MNP, WBC, CRP, and HNP1-3 in SF predicted the inflammatory processes with excellent diagnostic performance.

The authors concluded that SF biomarkers WBC, PMN, MNP CRP, HNP1-3, IL-1, IL-6, PMNE, and HLF2 allow the classification of new patients into the relevant SF group with an accuracy of 94.4%. In addition, WBC, PMN, MNP, CRP, and HNP1-3 provide excellent diagnostic sensitivity and specificity for the diagnosis of infection, despite the study including a limited number of patients with pyogenic and non-pyogenic inflammation. The study was originally published on line on March 15, 2021 in the Journal of Clinical Chemistry and Laboratory Medicine.

Related Links:
University of Ostrava
Beckman Coulter
Sysmex