Novel Biomarkers for Diagnosing Periprosthetic Joint Infection from Synovial Fluid and Serum

Abstract

Background: Synovial fluid bacterial culture is the cornerstone of confirmation or exclusion of periprosthetic joint infection (PJI). The aim of this study was to assess synovial fluid and serum biomarker patterns of patients with total joint arthroplasty (TJA), and the association of these patterns with PJI. Methods: Synovial fluid and serum samples were collected from 35 patients who were admitted to the Arthroplasty Unit of the Department of Orthopaedics and Traumatology at Turku University Hospital. Of the 25 patients who were included in the study, 10 healthy patients with an elective TJA for osteoarthritis served as the control group, and 15 patients who were admitted due to clinical suspicion of PJI with local redness, swelling, wound drainage, pain, and/or fever and who had a positive synovial fluid bacterial culture served as the study group. Logistic regression was used to assess the ability of 37 biomarkers (including cytokines, chemokines, and growth factors) with commercially available tests to detect PJIs. Results: In synovial fluid, the concentrations of sTNF-R1 and sTNF-R2 (soluble tumor necrosis factor receptors 1 and 2) and BAFF (B-cell activating factor, also known as TNFSF13B) were significantly higher in the PJI group (p < 0.002). In serum, the sTNF-R1 concentration was significantly higher in the PJI group, whereas the TWEAK (tumor necrosis factor-like weak inducer of apoptosis) and osteocalcin concentrations were significantly lower (p < 0.002). The sensitivity for detecting PJI using synovial fluid was 1.00 for sTNF-R2, 0.93 for sTNF-R1, and 0.87 for BAFF/TNFSF13B. The specificity of all 3 synovial markers was 1.00. The sensitivity using serum was 0.80 for TWEAK, 0.73 for sTNF-R1, and 0.80 for osteocalcin. The specificity of all 3 serum markers was 1.00. Conclusions: Synovial sTNF-R2 is a promising new biomarker for detecting PJI. We are not aware of any previous reports of the use of sTNF-R2 in PJI diagnosis. More research is needed to assess the clinical importance of our findings. Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

A 92 protein inflammation panel performed on sonicate fluid differentiates periprosthetic joint infection from non-infectious causes of arthroplasty failure

“…Interestingly, while each of these proteins is important for chemoattraction and inflammatory response of macrophages and neutrophils 66 , 84 – 86 , CCL20, as mentioned previously, and IL8 were present in higher levels in PJI compared to NIAF, while MCP-1 and CCL3 were present in lower levels in PJI compared to NIAF. While some identified proteins, including IL6, IL8, IL17A, IFNγ, and TWEAK have been found in synovial fluid or serum of subjects with PJI 22 , 27 , 30 , others, such as CCL20, OSM, EN-RAGE, and CXCL6, are more novel. Further investigation into the diagnostic power of these candidate biomarkers and potential for targeted treatment is needed.…”

What’s New in Musculoskeletal Infection

“…A number of specific biomarkers showed promise in the diagnosis of PJI, including synovial soluble tumor necrosis factor receptor 2 (sTNF-R2) 33 , synovial fluid interleukin-1 beta (IL-1β) (especially in combination with the polymorphonuclear [PMN] percentage) 34 , and calprotectin (of note, calprotectin did not reliably differentiate PJI from rheumatoid arthritis in this study) 35 . In 1 study, a calprotectin point-of-care test showed high sensitivity and specificity (>95%) in the diagnosis of PJI after TKA 36 .…”

Synovial calprotectin for the diagnosis of periprosthetic joint infection: a diagnostic meta-analysis

“…Biomarkers from blood and synovial fluid provide diagnose PJI with material evidence. For a host of researchers, much attention has been paid to discovering a novel and promising biomarker that has the potential to be a biomarker for diagnostic criteria compared with current ones [ 33 ]. Many researches show that synovial biomarkers are more useful than those from blood at accuracy diagnosis of PJI, such as α-defensin, interleukin-6, interleukin-1β, leukocyte esterase, and interleukin-17 [ 11 , 34 ].…”