Paper of the Week: A Clinical Pilot Study to Evaluate CD64 Expression on Blood Monocytes as an Indicator of Periprosthetic Joint Infection

Peng-Fei Qu, MD, Rui Li, MD, Chi Xu, MD, Wei Chai, MD, Hao Li, MD, Jun Fu, MD, and Ji-Ying Chen, MD

The Journal of Bone and Joint Surgery, Volume 102, Issue 17, pe 99, September 2, 2020
DOI: 10.2106/ JBJS.20.00057

Summary: Ilan Small, BS

Diagnosis of periprosthetic joint infection (PJI) relies upon blood inflammatory markers, joint fluid markers, intraoperative pathology samples, and fluid cultures (1, 2). Standard laboratory tests to diagnose PJI, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) maybe limited in value and additional markers need to be investigated (2). CD64 is a biomarker that has been used in the diagnosis of systemic and local infections and has been shown to have high diagnostic value (3). Qu et al. evaluated the diagnostic use of monocyte CD64 in a prospective study on patients undergoing joint revision. Flow cytometry was used to determine monocyte CD64 mean fluorescence intensity (mCD64MFI) and was internally validated prior to the study.

Sixty-two patients admitted to the Chinese PLA General Hospital for revision surgery were recruited for this study from August 2019 to December 2019. Of those 62 patients, 18 were diagnosed with PJI according to the modified MSIS criteria and 44 were placed into the non-PJI group. Fifteen patients in the PJI group had two positive periprosthetic cultures with phenotypically identical organisms and three had a sinus tract connecting with the infected joint. Three patients met four of the minor modified MSIS criteria; elevated CRP and ESR, elevated synovial fluid (SF) WBC, elevated percentage of SF neutrophils, positive histology of periprosthetic tissue, and a single positive culture.

The area under the curve (AUC) for mCD64MFI of 0.898 (95% CI, 0.821 – 0.975; p < 0.001), as compared to the AUC for ESR of 0.909 (95% CI, 0.812 – 1.000; p < 0.001) shows it can be used as a high diagnostic test for PJI. For mCD64MFI, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 1, 0.75, 0.62, and 1, respectively.

For nine patients with chronic PJI, the AUC for mCD64MFI was 0.889 (95% CI, 0.799 to 0.979; p < 0.001) as compared to 0.861 AUC for ESR (95% CI, 0.688 to 1.000; p < 0.001). For mCD64MFI, the respective sensitivity, specificity, PPV, and NPV were 1, 0.77, 0.47, and 1.

As a diagnostic tool for PJI, Qu et al. found CD64 to be of equal or greater diagnostic value than CRP and ESR. A blood test to measure mCD64MFI levels may be a quick and easy method to diagnose PJI. Limitations of the study included the small cohort, comorbidities affecting CD64 expression, short-term follow-up time, and single-center trial.

References:

1. Carli AV, Abdelbary H, Ahmadzai N, Cheng W, Shea B, Hutton B, Sniderman J, Philip Sanders BS, Esmaeilisaraji L, Skidmore B, Gauthier-Kwan OY, Bunting AC, Gauthier P, Crnic A, Logishetty K, Moher D, Fergusson D, Beaule ́ PE. Diagnostic accuracy of serum, synovial, and tissue testing for chronic periprosthetic joint infection after hip and knee replacements: a systematic review. J Bone Joint Surg Am. 2019 Apr 3;101(7):635-49.
2. Berbari E, Mabry T, Tsaras G, Spangehl M, Erwin PJ, Murad MH, Steckelberg J, Osmon D. Inflammatory blood laboratory levels as markers of prosthetic joint infection: a systematic review and meta-analysis. J Bone Joint Surg Am. 2010 Sep 1; 92(11):2102-9.
3. Farias MG, de Lucena NP, Dal Bo ́ S, de Castro SM. Neutrophil CD64 expression as an important diagnostic marker of infection and sepsis in hospital patients. J Immunol Methods. 2014 Dec 1;414:65-8. Epub 2014 Aug 30.