Joint fluid multi-omics improves diagnostic confidence during evaluation of children with presumed septic arthritis
Abstract Background An accurate diagnosis of septic versus reactive or autoimmune arthritis remains clinically challenging. A multi-omics strategy comprising metagenomic and proteomic technologies were undertaken for children diagnosed with presumed septic arthritis to advance clinical diagnoses and...
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BMC
2025-01-01
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| Series: | Pediatric Rheumatology Online Journal |
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| Online Access: | https://doi.org/10.1186/s12969-025-01060-z |
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| author | Yolanda Peña-López Naureen G. Tareen Bo Zhang Indu Raman Carlos A. Arana Chengsong Zhu Yang Liu Pratibha Selvakumar Nicolai S. C. van Oers Simrat Morris Lora V. Hooper Lawson A. B. Copley Prithvi Raj |
| author_facet | Yolanda Peña-López Naureen G. Tareen Bo Zhang Indu Raman Carlos A. Arana Chengsong Zhu Yang Liu Pratibha Selvakumar Nicolai S. C. van Oers Simrat Morris Lora V. Hooper Lawson A. B. Copley Prithvi Raj |
| author_sort | Yolanda Peña-López |
| collection | DOAJ |
| description | Abstract Background An accurate diagnosis of septic versus reactive or autoimmune arthritis remains clinically challenging. A multi-omics strategy comprising metagenomic and proteomic technologies were undertaken for children diagnosed with presumed septic arthritis to advance clinical diagnoses and care for affected individuals. Methods Twelve children with suspected septic arthritis were prospectively enrolled to compare standard of care tests with a rapid multi-omics approach. The multi-omics combined bacterial 16S rRNA metagenomics, single cell transcriptomics, and proteomics on knee joint fluid specimens. The diagnostic value of the multi-omics was ascertained relative to standard of care culture and PCR-negative results. Results Ten children with suspected primary septic arthritis and two with acute hematogenous osteomyelitis (AHO) diagnoses were assessed. Joint fluid bacterial cultures were positive for 6/12 (50%) patients, consistent with elevated inflammatory markers (IL-4, IL-6, IL-17A, TNF-a, etc.). Metagenomic bacterial sequencing results were 100% concordant with the culture results. Six patients were culture- and PCR-negative. Multiomics analyses of the 6 culture negative patients established that 2/6 culture-negative children had inflammatory arthritis with potential Juvenile idiopathic arthritis (JIA) and 1 had post-Streptococcal Reactive Arthritis. The children without any bacteremia had autoantibodies (IgGs) in the joint-fluid targeting several nuclear antigens (i.e., dsDNA, histones, Jo-1, scl-70, Ro/SS-A, SmDs, CENP-A along with non-nuclear antigens i.e. Albumin, Collagens, Myosin, Laminin, etc. Single cell transcriptomics confirmed an abundance of CD4+ follicular helper T (Tfh), CD8 + T cells and B cells in the autoantibody positive subjects. The combination of 16S DNA sequencing (p = 0.006), cytokine assays (p = 0.009) and autoantibody profiling (p = 0.02) were significantly distinct between those children with and without infections. This improved the diagnostic confidence for 9 of 12 (75%) children, key for treatment decisions. Conclusions The multiomics approach rapidly identified children with bacterial or autoimmune inflammatory conditions, improving diagnostic and treatment strategies for those with presumptive septic arthritis. |
| format | Article |
| id | doaj-art-a67a1f02827e4dfbb958a678c169865d |
| institution | Kabale University |
| issn | 1546-0096 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Pediatric Rheumatology Online Journal |
| spelling | doaj-art-a67a1f02827e4dfbb958a678c169865d2025-01-26T12:19:54ZengBMCPediatric Rheumatology Online Journal1546-00962025-01-0123111210.1186/s12969-025-01060-zJoint fluid multi-omics improves diagnostic confidence during evaluation of children with presumed septic arthritisYolanda Peña-López0Naureen G. Tareen1Bo Zhang2Indu Raman3Carlos A. Arana4Chengsong Zhu5Yang Liu6Pratibha Selvakumar7Nicolai S. C. van Oers8Simrat Morris9Lora V. Hooper10Lawson A. B. Copley11Prithvi Raj12Department of Immunology, University of Texas Southwestern Medical CenterDepartment of Pediatric Orthopaedic Surgery, Children’s Health System of TexasDepartment of Immunology, University of Texas Southwestern Medical CenterDepartment of Immunology, University of Texas Southwestern Medical CenterDepartment of Immunology, University of Texas Southwestern Medical CenterDepartment of Immunology, University of Texas Southwestern Medical CenterDepartment of Immunology, University of Texas Southwestern Medical CenterDepartment of Immunology, University of Texas Southwestern Medical CenterDepartment of Immunology, University of Texas Southwestern Medical CenterDivision of Rheumatology, Department of Pediatrics, UT Southwestern Medical CenterDepartment of Immunology, University of Texas Southwestern Medical CenterDepartment of Pediatric Orthopaedic Surgery, Children’s Health System of TexasDepartment of Immunology, University of Texas Southwestern Medical CenterAbstract Background An accurate diagnosis of septic versus reactive or autoimmune arthritis remains clinically challenging. A multi-omics strategy comprising metagenomic and proteomic technologies were undertaken for children diagnosed with presumed septic arthritis to advance clinical diagnoses and care for affected individuals. Methods Twelve children with suspected septic arthritis were prospectively enrolled to compare standard of care tests with a rapid multi-omics approach. The multi-omics combined bacterial 16S rRNA metagenomics, single cell transcriptomics, and proteomics on knee joint fluid specimens. The diagnostic value of the multi-omics was ascertained relative to standard of care culture and PCR-negative results. Results Ten children with suspected primary septic arthritis and two with acute hematogenous osteomyelitis (AHO) diagnoses were assessed. Joint fluid bacterial cultures were positive for 6/12 (50%) patients, consistent with elevated inflammatory markers (IL-4, IL-6, IL-17A, TNF-a, etc.). Metagenomic bacterial sequencing results were 100% concordant with the culture results. Six patients were culture- and PCR-negative. Multiomics analyses of the 6 culture negative patients established that 2/6 culture-negative children had inflammatory arthritis with potential Juvenile idiopathic arthritis (JIA) and 1 had post-Streptococcal Reactive Arthritis. The children without any bacteremia had autoantibodies (IgGs) in the joint-fluid targeting several nuclear antigens (i.e., dsDNA, histones, Jo-1, scl-70, Ro/SS-A, SmDs, CENP-A along with non-nuclear antigens i.e. Albumin, Collagens, Myosin, Laminin, etc. Single cell transcriptomics confirmed an abundance of CD4+ follicular helper T (Tfh), CD8 + T cells and B cells in the autoantibody positive subjects. The combination of 16S DNA sequencing (p = 0.006), cytokine assays (p = 0.009) and autoantibody profiling (p = 0.02) were significantly distinct between those children with and without infections. This improved the diagnostic confidence for 9 of 12 (75%) children, key for treatment decisions. Conclusions The multiomics approach rapidly identified children with bacterial or autoimmune inflammatory conditions, improving diagnostic and treatment strategies for those with presumptive septic arthritis.https://doi.org/10.1186/s12969-025-01060-zAutoimmuneCytokine Infection16S rRNA bacterial sequencingMetagenomicsNext-generation sequencing (NGS)Pediatric |
| spellingShingle | Yolanda Peña-López Naureen G. Tareen Bo Zhang Indu Raman Carlos A. Arana Chengsong Zhu Yang Liu Pratibha Selvakumar Nicolai S. C. van Oers Simrat Morris Lora V. Hooper Lawson A. B. Copley Prithvi Raj Joint fluid multi-omics improves diagnostic confidence during evaluation of children with presumed septic arthritis Pediatric Rheumatology Online Journal Autoimmune Cytokine Infection 16S rRNA bacterial sequencing Metagenomics Next-generation sequencing (NGS) Pediatric |
| title | Joint fluid multi-omics improves diagnostic confidence during evaluation of children with presumed septic arthritis |
| title_full | Joint fluid multi-omics improves diagnostic confidence during evaluation of children with presumed septic arthritis |
| title_fullStr | Joint fluid multi-omics improves diagnostic confidence during evaluation of children with presumed septic arthritis |
| title_full_unstemmed | Joint fluid multi-omics improves diagnostic confidence during evaluation of children with presumed septic arthritis |
| title_short | Joint fluid multi-omics improves diagnostic confidence during evaluation of children with presumed septic arthritis |
| title_sort | joint fluid multi omics improves diagnostic confidence during evaluation of children with presumed septic arthritis |
| topic | Autoimmune Cytokine Infection 16S rRNA bacterial sequencing Metagenomics Next-generation sequencing (NGS) Pediatric |
| url | https://doi.org/10.1186/s12969-025-01060-z |
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