Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. I...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00427/full |
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| author | Prathapan Ayyappan Robert Z. Harms Jennifer A. Seifert Elizabeth A. Bemis Marie L. Feser Kevin D. Deane M. Kristen Demoruelle Ted R. Mikuls V. Michael Holers Nora E. Sarvetnick Nora E. Sarvetnick |
| author_facet | Prathapan Ayyappan Robert Z. Harms Jennifer A. Seifert Elizabeth A. Bemis Marie L. Feser Kevin D. Deane M. Kristen Demoruelle Ted R. Mikuls V. Michael Holers Nora E. Sarvetnick Nora E. Sarvetnick |
| author_sort | Prathapan Ayyappan |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. Increased systemic bacterial exposure leads to elevated levels of antimicrobial response factors (ARFs) in the circulation. In the present study, we tested whether RA patients have increased levels of ARFs by analyzing the levels of multiple ARFs in serum from RA patients and healthy age and sex-matched controls. The levels of soluble CD14 (sCD14), lysozyme, and CXCL16 were significantly elevated in RA patients compared to healthy controls. Lipopolysaccharide binding protein (LBP) levels remained unchanged in RA patients compared to healthy controls. A positive correlation of LBP with rheumatoid factor (RF) was also found in RA subjects. Interestingly, the levels of anti-endotoxin core antibodies (EndoCAb) IgM, total IgM, EndoCAb IgA, and total IgA were significantly elevated in RA patients compared to healthy controls. No significant changes in the levels of EndoCAb IgG and total IgG were observed in RA patients compared to healthy controls. Furthermore, lysozyme and CXCL16 levels were positively correlated with disease severity among RA subjects. Increases in the levels of several ARFs and their correlations with clinical indices suggest systemic microbial exposure in the RA cohort. Modulation of microbial exposure may play an important role in disease pathogenesis in individuals with RA. |
| first_indexed | 2024-04-12T04:29:54Z |
| format | Article |
| id | doaj.art-547392a0899d44998b4eb8c047e4d725 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T04:29:54Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-547392a0899d44998b4eb8c047e4d7252022-12-22T03:47:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-03-011110.3389/fimmu.2020.00427513903Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid ArthritisPrathapan Ayyappan0Robert Z. Harms1Jennifer A. Seifert2Elizabeth A. Bemis3Marie L. Feser4Kevin D. Deane5M. Kristen Demoruelle6Ted R. Mikuls7V. Michael Holers8Nora E. Sarvetnick9Nora E. Sarvetnick10Department of Surgery-Transplant, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Surgery-Transplant, University of Nebraska Medical Center, Omaha, NE, United StatesDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, United StatesDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, United StatesDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, United StatesDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, United StatesDivision of Rheumatology, University of Nebraska Medical Center, Omaha, NE, United StatesDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, United StatesDepartment of Surgery-Transplant, University of Nebraska Medical Center, Omaha, NE, United StatesMary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, United StatesRheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. Increased systemic bacterial exposure leads to elevated levels of antimicrobial response factors (ARFs) in the circulation. In the present study, we tested whether RA patients have increased levels of ARFs by analyzing the levels of multiple ARFs in serum from RA patients and healthy age and sex-matched controls. The levels of soluble CD14 (sCD14), lysozyme, and CXCL16 were significantly elevated in RA patients compared to healthy controls. Lipopolysaccharide binding protein (LBP) levels remained unchanged in RA patients compared to healthy controls. A positive correlation of LBP with rheumatoid factor (RF) was also found in RA subjects. Interestingly, the levels of anti-endotoxin core antibodies (EndoCAb) IgM, total IgM, EndoCAb IgA, and total IgA were significantly elevated in RA patients compared to healthy controls. No significant changes in the levels of EndoCAb IgG and total IgG were observed in RA patients compared to healthy controls. Furthermore, lysozyme and CXCL16 levels were positively correlated with disease severity among RA subjects. Increases in the levels of several ARFs and their correlations with clinical indices suggest systemic microbial exposure in the RA cohort. Modulation of microbial exposure may play an important role in disease pathogenesis in individuals with RA.https://www.frontiersin.org/article/10.3389/fimmu.2020.00427/fullrheumatoid arthritisantimicrobial proteinsEndoCAbssCD14CXCL16lysozyme |
| spellingShingle | Prathapan Ayyappan Robert Z. Harms Jennifer A. Seifert Elizabeth A. Bemis Marie L. Feser Kevin D. Deane M. Kristen Demoruelle Ted R. Mikuls V. Michael Holers Nora E. Sarvetnick Nora E. Sarvetnick Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis Frontiers in Immunology rheumatoid arthritis antimicrobial proteins EndoCAbs sCD14 CXCL16 lysozyme |
| title | Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis |
| title_full | Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis |
| title_fullStr | Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis |
| title_full_unstemmed | Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis |
| title_short | Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis |
| title_sort | heightened levels of antimicrobial response factors in patients with rheumatoid arthritis |
| topic | rheumatoid arthritis antimicrobial proteins EndoCAbs sCD14 CXCL16 lysozyme |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00427/full |
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