PMID- 35306116 OWN - NLM STAT- MEDLINE DCOM- 20220412 LR - 20230531 IS - 1879-0038 (Electronic) IS - 0378-1119 (Print) IS - 0378-1119 (Linking) VI - 825 DP - 2022 May 30 TI - Human transcriptomic response to periprosthetic joint infection. PG - 146400 LID - S0378-1119(22)00219-0 [pii] LID - 10.1016/j.gene.2022.146400 [doi] AB - 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. CI - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Masters, Thao L AU - Masters TL AD - Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States. FAU - Bhagwate, Aditya V AU - Bhagwate AV AD - Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States. FAU - Dehankar, Mrunal K AU - Dehankar MK AD - Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States. FAU - Greenwood-Quaintance, Kerryl E AU - Greenwood-Quaintance KE AD - Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States. FAU - Abdel, Matthew P AU - Abdel MP AD - Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States. FAU - Mandrekar, Jay N AU - Mandrekar JN AD - Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States. FAU - Patel, Robin AU - Patel R AD - Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States; Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address: patel.robin@mayo.edu. LA - eng GR - R01 AR056647/AR/NIAMS NIH HHS/United States GR - T32 AR056950/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20220317 PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 0 (Biomarkers) RN - 0 (Colony-Stimulating Factors) RN - 0 (Interleukin-8) RN - 0 (Ligands) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - *Arthritis, Infectious/diagnosis/metabolism/microbiology MH - Biomarkers/analysis MH - Colony-Stimulating Factors MH - Humans MH - Interleukin-8 MH - Ligands MH - Matrix Metalloproteinase 3/metabolism MH - *Prosthesis-Related Infections/diagnosis/genetics MH - *Staphylococcal Infections/microbiology MH - Staphylococcus aureus/metabolism MH - Synovial Fluid/metabolism MH - Transcriptome MH - Vascular Endothelial Growth Factor A PMC - PMC9007914 MID - NIHMS1792307 OTO - NOTNLM OT - Biomarkers OT - Host response OT - Periprosthetic joint infection OT - RNA-Seq OT - Sonicate fluid EDAT- 2022/03/21 06:00 MHDA- 2022/04/13 06:00 PMCR- 2023/05/30 CRDT- 2022/03/20 20:27 PHST- 2021/01/25 00:00 [received] PHST- 2021/05/17 00:00 [revised] PHST- 2022/03/04 00:00 [accepted] PHST- 2022/03/21 06:00 [pubmed] PHST- 2022/04/13 06:00 [medline] PHST- 2022/03/20 20:27 [entrez] PHST- 2023/05/30 00:00 [pmc-release] AID - S0378-1119(22)00219-0 [pii] AID - 10.1016/j.gene.2022.146400 [doi] PST - ppublish SO - Gene. 2022 May 30;825:146400. doi: 10.1016/j.gene.2022.146400. Epub 2022 Mar 17.