The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity
IntroductionPeriodontitis is associated with rheumatoid arthritis (RA). One hypothesis posits that this connection arises from the formation of autoantibodies against citrullinated proteins (ACPA) in inflamed gums, possibly triggered by Porphyromonas gingivalis. We previously demonstrated an increas...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1504975/full |
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| author | Elin Kindstedt Elin Kindstedt Charlotte de Vries Magnus Wänman Barbara Aleksandra Potempa Jan Potempa Jan Potempa Susanne Lindquist Anders Esberg Karin Lundberg Pernilla Lundberg |
| author_facet | Elin Kindstedt Elin Kindstedt Charlotte de Vries Magnus Wänman Barbara Aleksandra Potempa Jan Potempa Jan Potempa Susanne Lindquist Anders Esberg Karin Lundberg Pernilla Lundberg |
| author_sort | Elin Kindstedt |
| collection | DOAJ |
| description | IntroductionPeriodontitis is associated with rheumatoid arthritis (RA). One hypothesis posits that this connection arises from the formation of autoantibodies against citrullinated proteins (ACPA) in inflamed gums, possibly triggered by Porphyromonas gingivalis. We previously demonstrated an increased antibody response to P. gingivalis arginine gingipains (anti-Rgp IgG), not only in individuals with severe periodontitis compared to controls, but in RA versus controls, with an association to ACPA. In the present study, we set out to further explore the relationship between anti-Rgp IgG, ACPA and periodontitis, including clinical periodontal parameters, in the large and well-characterized PerioGene North case-control study.MethodsWe measured serum levels of anti-Rgp and ACPA IgG by enzyme-linked immunosorbent assay (ELISA), in 478 patients with periodontitis and 509 periodontally healthy controls within PerioGene North. Subsequently, anti-Rgp IgG levels and ACPA status were analysed in relation to periodontitis and clinical periodontal parameters.ResultsSerum anti-Rgp IgG levels were elevated in cases versus controls (p< 0.001). However, receiver operating characteristic (ROC) curve analysis revealed that anti-Rgp IgG could not efficiently discriminate cases from controls (AUC= 0.63; 95% CI: 0.60 – 0.66). Among cases, increased anti-Rgp IgG levels associated with high periodontal inflammation and advanced alveolar bone loss (p<0.001 for both). An ACPA response was detected in 15 (3.1%) cases and 6 (1.2%) controls (p=0.033), but no association to periodontitis was evident after adjustment for age and smoking and anti-Rgp IgG levels did not differ between ACPA-positive and ACPA-negative individuals.ConclusionWe show that anti-Rgp IgG identifies a subgroup of periodontitis patients with high degree of periodontal inflammation and advanced alveolar bone loss, but we do not find support for a link between periodontitis or anti-Rgp IgG and ACPA status in PerioGene North. Given the association between anti-Rgp and alveolar bone loss, the mechanistic role of gingipains in bone resorption should be experimentally explored. |
| format | Article |
| id | doaj-art-be84d39bd7fc4f2199ccd7b6b41570f1 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-be84d39bd7fc4f2199ccd7b6b41570f12025-01-14T06:10:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15049751504975The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunityElin Kindstedt0Elin Kindstedt1Charlotte de Vries2Magnus Wänman3Barbara Aleksandra Potempa4Jan Potempa5Jan Potempa6Susanne Lindquist7Anders Esberg8Karin Lundberg9Pernilla Lundberg10Department of Odontology, Section for Molecular Periodontology, Umeå University, Umeå, SwedenWallenberg Centre for Molecular Medicine, Umeå University, Umeå, SwedenDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenDepartment of Odontology, Section for Molecular Periodontology, Umeå University, Umeå, SwedenDepartment of Oral Immunology & Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United StatesDepartment of Oral Immunology & Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United StatesDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandLipumAB, Umeå, SwedenDepartment of Odontology, Umeå University, Umeå, SwedenDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SwedenDepartment of Odontology, Section for Molecular Periodontology, Umeå University, Umeå, SwedenIntroductionPeriodontitis is associated with rheumatoid arthritis (RA). One hypothesis posits that this connection arises from the formation of autoantibodies against citrullinated proteins (ACPA) in inflamed gums, possibly triggered by Porphyromonas gingivalis. We previously demonstrated an increased antibody response to P. gingivalis arginine gingipains (anti-Rgp IgG), not only in individuals with severe periodontitis compared to controls, but in RA versus controls, with an association to ACPA. In the present study, we set out to further explore the relationship between anti-Rgp IgG, ACPA and periodontitis, including clinical periodontal parameters, in the large and well-characterized PerioGene North case-control study.MethodsWe measured serum levels of anti-Rgp and ACPA IgG by enzyme-linked immunosorbent assay (ELISA), in 478 patients with periodontitis and 509 periodontally healthy controls within PerioGene North. Subsequently, anti-Rgp IgG levels and ACPA status were analysed in relation to periodontitis and clinical periodontal parameters.ResultsSerum anti-Rgp IgG levels were elevated in cases versus controls (p< 0.001). However, receiver operating characteristic (ROC) curve analysis revealed that anti-Rgp IgG could not efficiently discriminate cases from controls (AUC= 0.63; 95% CI: 0.60 – 0.66). Among cases, increased anti-Rgp IgG levels associated with high periodontal inflammation and advanced alveolar bone loss (p<0.001 for both). An ACPA response was detected in 15 (3.1%) cases and 6 (1.2%) controls (p=0.033), but no association to periodontitis was evident after adjustment for age and smoking and anti-Rgp IgG levels did not differ between ACPA-positive and ACPA-negative individuals.ConclusionWe show that anti-Rgp IgG identifies a subgroup of periodontitis patients with high degree of periodontal inflammation and advanced alveolar bone loss, but we do not find support for a link between periodontitis or anti-Rgp IgG and ACPA status in PerioGene North. Given the association between anti-Rgp and alveolar bone loss, the mechanistic role of gingipains in bone resorption should be experimentally explored.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1504975/fullperiodontitisalveolar bone lossperiodontal inflammationcysteine peptidase gingipain Banti-citrullinated protein antibodies |
| spellingShingle | Elin Kindstedt Elin Kindstedt Charlotte de Vries Magnus Wänman Barbara Aleksandra Potempa Jan Potempa Jan Potempa Susanne Lindquist Anders Esberg Karin Lundberg Pernilla Lundberg The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity Frontiers in Immunology periodontitis alveolar bone loss periodontal inflammation cysteine peptidase gingipain B anti-citrullinated protein antibodies |
| title | The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity |
| title_full | The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity |
| title_fullStr | The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity |
| title_full_unstemmed | The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity |
| title_short | The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity |
| title_sort | periogene north study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity |
| topic | periodontitis alveolar bone loss periodontal inflammation cysteine peptidase gingipain B anti-citrullinated protein antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1504975/full |
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