Differences between infected and noninfected synovial fluid

Abstract

Aims The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF. Methods In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups. Results A total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine). Conclusion Metabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF. Cite this article: Bone Joint Res 2021;10(1):85–95.

Application of 68Ga-citrate PET/CT for differentiating periprosthetic joint infection from aseptic loosening after joint replacement surgery

“…However, the detection of the causative pathogen still relies mostly on conventional microbial culture, and the main demerit of preoperative puncture bacterial culture is that it is time-consuming, and the positive rate of culture is low. 22,23 Several methods can be used in the preoperative diagnosis of PJI and AL, including laboratory tests for inflammatory biomarkers, 24,25 synovial fluid marker tests, [23][24][25][26][27][28][29][30][31] and imaging examination. 4,12,18,19,[32][33][34][35][36][37][38][39] Recently, promising results have been reported regarding synovial biomarker tests, including the neutrophil CD64 index, synovial interleukin (IL)-6 measurement, metagenomic next-generation sequencing, enzyme-linked immunosorbent assay (ELISA) methods to detect the concentration of calprotectin, RNA-based transcription-quantitative polymerase chain reaction method, and lateral flow test.…”

“…4,12,18,19,[32][33][34][35][36][37][38][39] Recently, promising results have been reported regarding synovial biomarker tests, including the neutrophil CD64 index, synovial interleukin (IL)-6 measurement, metagenomic next-generation sequencing, enzyme-linked immunosorbent assay (ELISA) methods to detect the concentration of calprotectin, RNA-based transcription-quantitative polymerase chain reaction method, and lateral flow test. [23][24][25][26][27][28][29][30][31] Although these studies show that the above indices or methods perform well in identifying infected and non-infectious lesions, there were some limitations, including lack of practical experience in large samples, unavailability of the assays in some laboratories, and conflicts between different studies, which make the test results difficult to interpret. At present, preoperative noninvasive imaging examination is an attractive method, wherein nuclear medical examination, which can reflect functional changes, has unique advantages.…”

Differential metabolism between biofilm and suspended Pseudomonas aeruginosa cultures in bovine synovial fluid by 2D NMR-based metabolomics

“…but not yet to investigate the potential for P. aeruginosa or biofilm specific metabolites (9)(10)(11)(12).…”

Estudo do perfil metabólico do líquido sinovial de pacientes com infecção periprotética do joelho

“…A metabolômica, ao realizar o estudo sistemático dos produtos finais dos processos celulares (metabólitos), tem se tornado uma importante ferramenta para o entendimento da resposta do organismo a diversas doenças, e tem sido empregada para o desenvolvimento de testes diagnósticos e, também, preditores de prognóstico ou de acompanhamento em diversas patologias, tais como: sepse, câncer, insuficiência cardíaca, síndromes metabólicas e diversas doenças infecciosas (156,(159)(160)(161)163).…”

“…Nessa abordagem, o objetivo não é a quantificação absoluta dos metabólitos em si, mas a identificação dos metabólitos alterados pela condição estudada. Após a identificação dos potenciais biomarcadores, a metabolômica direcionada pode ser utilizada para validação dos resultados (163,164,168,169). A abordagem direcionada é, geralmente, usada para testar uma hipótese previamente formulada em que apenas um conjunto específico de metabólitos, relativos à pergunta investigada, é avaliado (Figura 1) (25,160,170).…”