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High-Dimensional Analysis of Immune Cell Composition Predicts Periprosthetic Joint Infections and Dissects Its Pathophysiology.

ABSTRACT: Accurate diagnosis of periprosthetic joint infections (PJI) is one of the most widely researched areas in modern orthopedic endoprosthesis. However, our understanding of the immunological basis of this severe complication is still limited. In this study, we developed a flow cytometric approach to precisely characterize the immune cell composition in periprosthetic joints. Using high-dimensional multi-parametric data, we defined, for the first time, the local immune cell populations of artificial joints. We identified significant differences in the cellular distribution between infected and non-infected samples, and revealed that myeloid-derived suppressor cells (MDSCs) act as potential regulators of infiltrating immune cells in PJI. Further, we developed an algorithm to predict septic and aseptic samples with high sensitivity and specificity, that may serve as an indispensable addition to the current criteria of the Musculoskeletal Infection Society. This study describes a novel approach to flow cytometrically analyze the immune cell infiltrate of joint fluid that not only improves our understanding of the pathophysiology of PJI, but also enables the development of a novel screening tool to predict infection status. Our data further suggest that pharmacological targeting of MDSCs represents a novel strategy for addressing PJI.

SUBMITTER: Korn MF

PROVIDER: S-EPMC7554968 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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High-Dimensional Analysis of Immune Cell Composition Predicts Periprosthetic Joint Infections and Dissects Its Pathophysiology.

Korn Maximilian F MF Stein Richard R RR Dolf Andreas A Shakeri Farhad F Buness Andreas A Hilgers Cäcilia C Masson Werner W Gravius Sascha S Kohlhof Hendrik H Burger Christof C Wirtz Dieter C DC Randau Thomas M TM Schildberg Frank A FA

Biomedicines 20200917 9

Accurate diagnosis of periprosthetic joint infections (PJI) is one of the most widely researched areas in modern orthopedic endoprosthesis. However, our understanding of the immunological basis of this severe complication is still limited. In this study, we developed a flow cytometric approach to precisely characterize the immune cell composition in periprosthetic joints. Using high-dimensional multi-parametric data, we defined, for the first time, the local immune cell populations of artificial ...[more]

PMID: 32957521

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Project description:Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure. We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure. Differential gene expression analysis confirmed 28 previously reported potential biomarkers of PJI, including bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), C-C-motif chemokine ligand 3 (CCL3), 4(CCL4), and C-X-C-motif chemokine ligand 2 (CXCL2), colony stimulating factor 2 receptor beta (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), Fc fragment of IgG receptor 1B (CD64B), intercellular adhesion molecule 1 (ICAM1), interferon gamma (IFNG), interleukin 13 receptor subunit alpha 2 (IL13RA2), interleukin 17D (IL17D), interleukin 1 (IL1A, IL1B, IL1RN), interleukin 2 receptors (IL2RA, IL2RG), interleukin 5 receptor (IL5RA), interleukin 6 (IL6), interleukin 8 (IL8), lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), and identified three novel molecules of potential diagnostic use for detection of PJI, namely C-C-motif chemokine ligand CCL20, coagulation factor VII (F7), and B cell receptor FCRL4. Comparative analysis of infections caused by staphylococci versus bacteria other than staphylococci and Staphylococcus aureus versus Staphylococcus epidermidis showed elevated expression of interleukin 13 (IL13), IL17D, and MMP3 in staphylococcal infections, and of IL1B, IL8, and platelet factor PF4V1 in S. aureus compared to S. epidermidis infections. Pathway analysis of over-represented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents. The data presented provides new potential targets for diagnosis of PJI and for differentiation of PJI caused by different infectious agents.

Dataset Information

High-Dimensional Analysis of Immune Cell Composition Predicts Periprosthetic Joint Infections and Dissects Its Pathophysiology.

Publications

High-Dimensional Analysis of Immune Cell Composition Predicts Periprosthetic Joint Infections and Dissects Its Pathophysiology.

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