The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis
Abstract Background Dysbiotic intestinal and oral microbiota have been implicated in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms how microbiota could impact disease activity have remained elusive. The aim of this study was to assess the association of the biological activity of...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-11-01
|
| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02946-z |
| _version_ | 1828119806043226112 |
|---|---|
| author | J. Parantainen G. Barreto R. Koivuniemi H. Kautiainen D. Nordström E. Moilanen M. Hämäläinen M. Leirisalo-Repo K. Nurmi K. K. Eklund |
| author_facet | J. Parantainen G. Barreto R. Koivuniemi H. Kautiainen D. Nordström E. Moilanen M. Hämäläinen M. Leirisalo-Repo K. Nurmi K. K. Eklund |
| author_sort | J. Parantainen |
| collection | DOAJ |
| description | Abstract Background Dysbiotic intestinal and oral microbiota have been implicated in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms how microbiota could impact disease activity have remained elusive. The aim of this study was to assess the association of the biological activity of serum lipopolysaccharides (LPS) with disease activity and likelihood of achieving remission in RA patients. Methods We measured Toll-like receptor (TLR) 4-stimulating activity of sera of 58 RA patients with a reporter cell line engineered to produce secreted alkaline phosphatase in response to TLR4 stimulation. Levels of LPS-binding protein, CD14, and CD163 were determined by ELISA assays. Results The patient serum-induced TLR4 activation (biological activity of LPS) was significantly associated with inflammatory parameters and body mass index at baseline and at 12 months and with disease activity (DAS28-CRP, p<0.001) at 12 months. Importantly, baseline LPS bioactivity correlated with disease activity (p=0.031) and, in 28 early RA patients, the likelihood of achieving remission at 12 months (p=0.009). The level of LPS bioactivity was similar at baseline and 12-month visits, suggesting that LPS bioactivity is an independent patient-related factor. Neutralization of LPS in serum by polymyxin B abrogated the TLR4 signaling, suggesting that LPS was the major contributor to TLR4 activation. Conclusion We describe a novel approach to study the biological activity of serum LPS and their impact in diseases. The results suggest that LPS contribute to the inflammatory burden and disease activity on patients with RA and that serum-induced TLR4 activation assays can serve as an independent prognostic factor. Graphical Abstract A graphical summary of the conclusions of the study. |
| first_indexed | 2024-04-11T13:53:49Z |
| format | Article |
| id | doaj.art-816e8f97ea8b4e0084d5f79d763f2d51 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-11T13:53:49Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-816e8f97ea8b4e0084d5f79d763f2d512022-12-22T04:20:24ZengBMCArthritis Research & Therapy1478-63622022-11-0124111010.1186/s13075-022-02946-zThe biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritisJ. Parantainen0G. Barreto1R. Koivuniemi2H. Kautiainen3D. Nordström4E. Moilanen5M. Hämäläinen6M. Leirisalo-Repo7K. Nurmi8K. K. Eklund9Translational Immunology Research Program, Faculty of Medicine, University of HelsinkiTranslational Immunology Research Program, Faculty of Medicine, University of HelsinkiDepartment of Rheumatology, Inflammation Center, University of Helsinki and Helsinki University HospitalFolkhälsan Research Center, Helsinki, Finland; Unit of Primary Health Care, Kuopio University HospitalDepartment of Internal medicine and rehabilitation, Helsinki University and Helsinki University HospitalThe Immunopharmacology Research Group, Faculty of Medicine and Health Technology, University of Tampere and Tampere University HospitalThe Immunopharmacology Research Group, Faculty of Medicine and Health Technology, University of Tampere and Tampere University HospitalDepartment of Rheumatology, Inflammation Center, University of Helsinki and Helsinki University HospitalTranslational Immunology Research Program, Faculty of Medicine, University of HelsinkiTranslational Immunology Research Program, Faculty of Medicine, University of HelsinkiAbstract Background Dysbiotic intestinal and oral microbiota have been implicated in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms how microbiota could impact disease activity have remained elusive. The aim of this study was to assess the association of the biological activity of serum lipopolysaccharides (LPS) with disease activity and likelihood of achieving remission in RA patients. Methods We measured Toll-like receptor (TLR) 4-stimulating activity of sera of 58 RA patients with a reporter cell line engineered to produce secreted alkaline phosphatase in response to TLR4 stimulation. Levels of LPS-binding protein, CD14, and CD163 were determined by ELISA assays. Results The patient serum-induced TLR4 activation (biological activity of LPS) was significantly associated with inflammatory parameters and body mass index at baseline and at 12 months and with disease activity (DAS28-CRP, p<0.001) at 12 months. Importantly, baseline LPS bioactivity correlated with disease activity (p=0.031) and, in 28 early RA patients, the likelihood of achieving remission at 12 months (p=0.009). The level of LPS bioactivity was similar at baseline and 12-month visits, suggesting that LPS bioactivity is an independent patient-related factor. Neutralization of LPS in serum by polymyxin B abrogated the TLR4 signaling, suggesting that LPS was the major contributor to TLR4 activation. Conclusion We describe a novel approach to study the biological activity of serum LPS and their impact in diseases. The results suggest that LPS contribute to the inflammatory burden and disease activity on patients with RA and that serum-induced TLR4 activation assays can serve as an independent prognostic factor. Graphical Abstract A graphical summary of the conclusions of the study.https://doi.org/10.1186/s13075-022-02946-zRheumatoid arthritisLipopolysaccharidesDysbiosis |
| spellingShingle | J. Parantainen G. Barreto R. Koivuniemi H. Kautiainen D. Nordström E. Moilanen M. Hämäläinen M. Leirisalo-Repo K. Nurmi K. K. Eklund The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis Arthritis Research & Therapy Rheumatoid arthritis Lipopolysaccharides Dysbiosis |
| title | The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis |
| title_full | The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis |
| title_fullStr | The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis |
| title_full_unstemmed | The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis |
| title_short | The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis |
| title_sort | biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis |
| topic | Rheumatoid arthritis Lipopolysaccharides Dysbiosis |
| url | https://doi.org/10.1186/s13075-022-02946-z |
| work_keys_str_mv | AT jparantainen thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT gbarreto thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT rkoivuniemi thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT hkautiainen thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT dnordstrom thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT emoilanen thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT mhamalainen thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT mleirisalorepo thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT knurmi thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT kkeklund thebiologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT jparantainen biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT gbarreto biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT rkoivuniemi biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT hkautiainen biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT dnordstrom biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT emoilanen biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT mhamalainen biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT mleirisalorepo biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT knurmi biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis AT kkeklund biologicalactivityofserumbacteriallipopolysaccharidesassociateswithdiseaseactivityandlikelihoodofachievingremissioninpatientswithrheumatoidarthritis |