Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections

Abstract

Objectives Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. Methods We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. Results Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. Conclusion IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement. Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179–188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1.

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

“…We confirmed that SF IL-16 can be used as a biomarker for PJI diagnosis [10]. To date, no studies have reported the possible effects of IL-16 on bone.…”

“…Abu-Ame [41] confirmed that LPS-induced osteoclastogenesis is mediated by TNF or its p55 receptor in vivo. Because we detected increased IL-16 levels in patients with PJI [10], whether IL-16 inhibition improves GN bacterial infection-associated bone loss warrants further study. In this study, the anti-IL-16 antibody treatment prevented LPS-induced trabecular bone loss and osteoclast activation in vivo.…”

“…PJI was diagnosed using the Musculoskeletal Infection Society (MSIS) criteria and was analyzed using the available evidence [42]. For a detailed description of PJI diagnostic methods, please refer to our previous articles [10,43]. All patients with PJI were scheduled to receive two-stage exchange arthroplasty.…”

“…Periprosthetic joint infection (PJI) is the most common cause of knee arthroplasty failure which accounts for 16% to 25% of all failed knee replacements [1][2][3][4] and is the third most common indication for revision hip arthroplasty [5][6][7][8][9]. Our previous findings indicated that the expression level of synovial fluid (SF) interleukin-16 (IL-16) in patients with PJI was higher than that in patients with aseptic loosening [10]. IL-16 returned to baseline values after debridement.…”

Current Clinical Methods for Detection of Peri-Prosthetic Joint Infection

“…This is the reason other ILs such as IL-16, IL-18, and cysteine rich with EGF-like domains 2 (CRELD2) are being investigated as better indicators. Chen et al [46] found that IL-16 and IL-18 and CRELD2 had statistical significance as overall better indicators in PJI detection than CRP and leukocyte count.…”