Abstract
ABSTRACTThe timely and exact diagnosis of prosthetic joint infection (PJI) is crucial for surgical decision-making. Intraoperatively, delivery of the result within an hour is required. Alpha-defensin lateral immunoassay of joint fluid (JF) is precise for the intraoperative exclusion of PJI; however, for patients with a limited amount of JF and/or in cases where the JF is bloody, this test is unhelpful. Important information is hidden in periprosthetic tissues that may much better reflect the current status of implant pathology. We therefore investigated the utility of the gene expression patterns of 12 candidate genes (TLR1, -2, -4, -6, and 10, DEFA1, LTF, IL1B, BPI, CRP, IFNG, and DEFB4A) previously associated with infection for detection of PJI in periprosthetic tissues of patients with total joint arthroplasty (TJA) (n = 76) reoperated for PJI (n = 38) or aseptic failure (n = 38), using the ultrafast quantitative reverse transcription-PCR (RT-PCR) Xxpress system (BJS Biotechnologies Ltd.). Advanced data-mining algorithms were applied for data analysis. For PJI, we detected elevated mRNA expression levels of DEFA1 (P < 0.0001), IL1B (P < 0.0001), LTF (P < 0.0001), TLR1 (P = 0.02), and BPI (P = 0.01) in comparison to those in tissues from aseptic cases. A feature selection algorithm revealed that the DEFA1-IL1B-LTF pattern was the most appropriate for detection/exclusion of PJI, achieving 94.5% sensitivity and 95.7% specificity, with likelihood ratios (LRs) for positive and negative results of 16.3 and 0.06, respectively. Taken together, the results show that DEFA1-IL1B-LTF gene expression detection by use of ultrafast qRT-PCR linked to an electronic calculator allows detection of patients with a high probability of PJI within 45 min after sampling. Further testing on a larger cohort of patients is needed.
Highlights
The timely and exact diagnosis of prosthetic joint infection (PJI) is crucial for surgical decision-making
In order to determine PJI-associated gene expression patterns in periprosthetic tissues, we compared gene expression levels of 12 candidate molecules (TLR1, -2, -4, -6, and -10, DEFA1, LTF, IL1B, BPI, CRP, IFNG, and DEFB4A) previously reported as potential biomarkers for detection of PJI in tissues obtained from patients with total joint arthroplasty (TJA) during revision surgery
Among the studied genes, enhanced gene expression of DEFA1 (P Ͻ 0.0001), IL1B (P Ͻ 0.0001), LTF (P Ͻ 0.0001), TLR1 (P ϭ 0.02), and BPI (P ϭ 0.01) was detected for patients with clinically proven PJI compared to that for patients with aseptic loosening (AL) by use of the RotorGene Q system; in addition, high interindividual variability was detected in the patient subgroups (Fig. 1; Table 1)
Summary
The timely and exact diagnosis of prosthetic joint infection (PJI) is crucial for surgical decision-making. Gene Pattern for PJI Diagnostics removal of the implant on the basis of the appearance of periprosthetic tissues and/or joint fluid, regardless of the results of preoperative tests Taken together, these instances indicate that there is a strong requirement for a diagnostic tool that is exact and available in a timely manner for the intraoperative exclusion of PJI. There is evidence of the usefulness of the leukocyte-esterase test and, especially, the alpha-defensin lateral immunoassay for the intraoperative exclusion of PJI, both of which deliver results within 10 min [4] These tests have wellknown limitations in terms of the required working conditions (e.g., the minimum amount of joint fluid needed and a problem with blood interference) and the generation of false-positive and/or false-negative results [5,6,7,8]. It was reported that gene profiling of periprosthetic tissues may allow the proposal of novel PJI biomarkers, as shown for TLR1 [11]
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