Porphyromonas gingivalis associates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk population
Objective The antibody response against Porphyromonas gingivalis (Pg) is elevated in rheumatoid arthritis (RA), especially in patients with anti-citrullinated protein antibodies (ACPA). Here, we investigated whether antibodies against the Pg virulence factor arginine gingipain (Rgp) are associated w...
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BMJ Publishing Group
2025-01-01
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| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/11/1/e005111.full |
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| author | Helga Westerlind Linda Mathsson-Alm Alexandra Circiumaru Aase Hensvold Karin Lundberg Jan Potempa Yogan Kisten Charlotte De Vries Marina Dehara Barbara Potempa |
| author_facet | Helga Westerlind Linda Mathsson-Alm Alexandra Circiumaru Aase Hensvold Karin Lundberg Jan Potempa Yogan Kisten Charlotte De Vries Marina Dehara Barbara Potempa |
| author_sort | Helga Westerlind |
| collection | DOAJ |
| description | Objective The antibody response against Porphyromonas gingivalis (Pg) is elevated in rheumatoid arthritis (RA), especially in patients with anti-citrullinated protein antibodies (ACPA). Here, we investigated whether antibodies against the Pg virulence factor arginine gingipain (Rgp) are associated with the RA-risk phase and development of arthritis.Methods At-risk individuals were included in a prospective study (Risk-RA) based on a positive anti-cyclic citrullinated peptide 2 (CCP2) antibody test, and having musculoskeletal complaints but no signs of arthritis. Study participants were followed for ≥3 years (arthritis-free, n=165) or until arthritis onset (progressors, n=95). Anti-Rgp IgG was measured in Risk-RA (260 baseline and 247 follow-up samples) and healthy controls (n=126); anti-CCP2 IgG was measured in Risk-RA (254 baseline samples). Data were analysed in GraphPad Prism and R using log-transformed antibody levels.Results 53% of Risk-RA and 26% of controls, p=0.003, were anti-Rgp IgG positive at baseline, with higher levels in Risk-RA compared with controls, p<0.0001. No changes in anti-Rgp IgG levels were observed during follow-up. The anti-Rgp IgG response at baseline did not associate with the development of arthritis; Cox-regression showed an HR of 0.95 (CI 0.80 to 1.13, p=0.6) for anti-Rgp IgG levels, and 0.82 (CI 0.55 to 1.23, p=0.3) for anti-Rgp IgG positivity.Conclusions Antibodies against the oral bacterium Pg are elevated during the RA-risk phase, both in individuals progressing to arthritis and in individuals remaining arthritis-free. Hence, Pg infection can be linked to the presence of RA-specific autoimmunity, ACPA, and musculoskeletal symptoms, but not to further development of arthritis in this at-risk population. |
| format | Article |
| id | doaj-art-1c44d097e61942f5bddbb54f15f18a97 |
| institution | Kabale University |
| issn | 2056-5933 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj-art-1c44d097e61942f5bddbb54f15f18a972025-02-01T05:20:09ZengBMJ Publishing GroupRMD Open2056-59332025-01-0111110.1136/rmdopen-2024-005111Porphyromonas gingivalis associates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk populationHelga Westerlind0Linda Mathsson-Alm1Alexandra Circiumaru2Aase Hensvold3Karin Lundberg4Jan Potempa5Yogan Kisten6Charlotte De Vries7Marina Dehara8Barbara Potempa9Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenDepartment of Oral Immunology & Infectious Diseases, School of Dentistry, University of Louisville, Louisville, Kentucky, USADivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenClinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, SwedenDepartment of Oral Immunology & Infectious Diseases, School of Dentistry, University of Louisville, Louisville, Kentucky, USAObjective The antibody response against Porphyromonas gingivalis (Pg) is elevated in rheumatoid arthritis (RA), especially in patients with anti-citrullinated protein antibodies (ACPA). Here, we investigated whether antibodies against the Pg virulence factor arginine gingipain (Rgp) are associated with the RA-risk phase and development of arthritis.Methods At-risk individuals were included in a prospective study (Risk-RA) based on a positive anti-cyclic citrullinated peptide 2 (CCP2) antibody test, and having musculoskeletal complaints but no signs of arthritis. Study participants were followed for ≥3 years (arthritis-free, n=165) or until arthritis onset (progressors, n=95). Anti-Rgp IgG was measured in Risk-RA (260 baseline and 247 follow-up samples) and healthy controls (n=126); anti-CCP2 IgG was measured in Risk-RA (254 baseline samples). Data were analysed in GraphPad Prism and R using log-transformed antibody levels.Results 53% of Risk-RA and 26% of controls, p=0.003, were anti-Rgp IgG positive at baseline, with higher levels in Risk-RA compared with controls, p<0.0001. No changes in anti-Rgp IgG levels were observed during follow-up. The anti-Rgp IgG response at baseline did not associate with the development of arthritis; Cox-regression showed an HR of 0.95 (CI 0.80 to 1.13, p=0.6) for anti-Rgp IgG levels, and 0.82 (CI 0.55 to 1.23, p=0.3) for anti-Rgp IgG positivity.Conclusions Antibodies against the oral bacterium Pg are elevated during the RA-risk phase, both in individuals progressing to arthritis and in individuals remaining arthritis-free. Hence, Pg infection can be linked to the presence of RA-specific autoimmunity, ACPA, and musculoskeletal symptoms, but not to further development of arthritis in this at-risk population.https://rmdopen.bmj.com/content/11/1/e005111.full |
| spellingShingle | Helga Westerlind Linda Mathsson-Alm Alexandra Circiumaru Aase Hensvold Karin Lundberg Jan Potempa Yogan Kisten Charlotte De Vries Marina Dehara Barbara Potempa Porphyromonas gingivalis associates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk population RMD Open |
| title | Porphyromonas gingivalis associates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk population |
| title_full | Porphyromonas gingivalis associates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk population |
| title_fullStr | Porphyromonas gingivalis associates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk population |
| title_full_unstemmed | Porphyromonas gingivalis associates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk population |
| title_short | Porphyromonas gingivalis associates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk population |
| title_sort | porphyromonas gingivalis associates with the presence of anti citrullinated protein antibodies but not with the onset of arthritis studies in an at risk population |
| url | https://rmdopen.bmj.com/content/11/1/e005111.full |
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