A potential role for chlamydial infection in rheumatoid arthritis development
To assess the relationship between self-reported and serological evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA development. This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA...
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| Veröffentlicht in: | Rheumatology (Oxford, England) England), 2025-01, Vol.64 (1), p.252-260 |
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| creator | Lamacchia, Celine Aymon, Romain Hattel, Brian C Aeby, Sebastien Kebbi-Beghdadi, Carole Gilbert, Benoit Studer, Olivia Norris, Jill M Nolers, V Michael Demoruelle, M Kristen Feser, Marie L Moss, Laura Kay Courvoisier, Delphine S Lauper, Kim Deane, Kevin D Greub, Gilbert Finckh, Axel |
| description | To assess the relationship between self-reported and serological evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA development.
This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a questionnaire on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA autoimmunity, RA-associated symptoms and RA autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against the major outer membrane protein of Chlamydia trachomatis. We replicated our analysis in an independent USA-based RA-FDR cohort.
Among 1231 RA-FDRs, 168 (13.6%) developed RA autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA autoimmunity compared with controls (17.9% vs 9.8%, odds ratio [OR] = 2.00; 95% CI: 1.27, 3.09; P |
| doi_str_mv | 10.1093/rheumatology/kead682 |
| format | Article |
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This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a questionnaire on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA autoimmunity, RA-associated symptoms and RA autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against the major outer membrane protein of Chlamydia trachomatis. We replicated our analysis in an independent USA-based RA-FDR cohort.
Among 1231 RA-FDRs, 168 (13.6%) developed RA autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA autoimmunity compared with controls (17.9% vs 9.8%, odds ratio [OR] = 2.00; 95% CI: 1.27, 3.09; P < 0.01). This association remained significant after adjustments (OR = 1.91; 95% CI: 1.20, 2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA autoimmunity (OR = 3.05; 95% CI: 1.10, 8.46; P = 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity.
Self-reported chlamydial infections are associated with elevated RA autoimmunity in at-risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies, but is consistent with a role of mucosal origin of RA-related autoimmunity.</description><identifier>ISSN: 1462-0324</identifier><identifier>ISSN: 1462-0332</identifier><identifier>EISSN: 1462-0332</identifier><identifier>DOI: 10.1093/rheumatology/kead682</identifier><identifier>PMID: 38092030</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Clinical Science</subject><ispartof>Rheumatology (Oxford, England), 2025-01, Vol.64 (1), p.252-260</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c288t-e2a8a28c0b47d1bbb0f637a379d346d06a0594218c1db2785eb06026c21ab73d3</cites><orcidid>0000-0002-1956-2607 ; 0000-0002-0291-8865 ; 0000-0002-4315-9009 ; 0000-0003-2211-4861</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38092030$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lamacchia, Celine</creatorcontrib><creatorcontrib>Aymon, Romain</creatorcontrib><creatorcontrib>Hattel, Brian C</creatorcontrib><creatorcontrib>Aeby, Sebastien</creatorcontrib><creatorcontrib>Kebbi-Beghdadi, Carole</creatorcontrib><creatorcontrib>Gilbert, Benoit</creatorcontrib><creatorcontrib>Studer, Olivia</creatorcontrib><creatorcontrib>Norris, Jill M</creatorcontrib><creatorcontrib>Nolers, V Michael</creatorcontrib><creatorcontrib>Demoruelle, M Kristen</creatorcontrib><creatorcontrib>Feser, Marie L</creatorcontrib><creatorcontrib>Moss, Laura Kay</creatorcontrib><creatorcontrib>Courvoisier, Delphine S</creatorcontrib><creatorcontrib>Lauper, Kim</creatorcontrib><creatorcontrib>Deane, Kevin D</creatorcontrib><creatorcontrib>Greub, Gilbert</creatorcontrib><creatorcontrib>Finckh, Axel</creatorcontrib><title>A potential role for chlamydial infection in rheumatoid arthritis development</title><title>Rheumatology (Oxford, England)</title><addtitle>Rheumatology (Oxford)</addtitle><description>To assess the relationship between self-reported and serological evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA development.
This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a questionnaire on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA autoimmunity, RA-associated symptoms and RA autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against the major outer membrane protein of Chlamydia trachomatis. We replicated our analysis in an independent USA-based RA-FDR cohort.
Among 1231 RA-FDRs, 168 (13.6%) developed RA autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA autoimmunity compared with controls (17.9% vs 9.8%, odds ratio [OR] = 2.00; 95% CI: 1.27, 3.09; P < 0.01). This association remained significant after adjustments (OR = 1.91; 95% CI: 1.20, 2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA autoimmunity (OR = 3.05; 95% CI: 1.10, 8.46; P = 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity.
Self-reported chlamydial infections are associated with elevated RA autoimmunity in at-risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies, but is consistent with a role of mucosal origin of RA-related autoimmunity.</description><subject>Clinical Science</subject><issn>1462-0324</issn><issn>1462-0332</issn><issn>1462-0332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><recordid>eNpVUctOwzAQtBCIlsIfIJQjl9C1nYdzQlXFSyriAmfLsZ3G4MTFTir170nVh8ppR7uzM6sdhG4xPGAo6NTXum9E56xbbqY_WqiMkTM0xklGYqCUnB8xSUboKoRvAEgxZZdoRBkUBCiM0fssWrlOt50RNvLO6qhyPpK1Fc1GbXumrbTsjGsHFB08jYqE72pvOhMipdfaulUziFyji0rYoG_2dYK-np8-56_x4uPlbT5bxJIw1sWaCCYIk1AmucJlWUKV0VzQvFA0yRRkAtIiIZhJrEqSs1SXkAHJJMGizKmiE_S40131ZaOVHKy9sHzlTSP8hjth-P9Ja2q-dGuOcQ6YYhgU7vcK3v32OnS8MUFqa0WrXR84KYAUOSFZOlCTHVV6F4LX1dEHA99GwU-j4PsohrW70xuPS4ff0z_ir4xC</recordid><startdate>20250101</startdate><enddate>20250101</enddate><creator>Lamacchia, Celine</creator><creator>Aymon, Romain</creator><creator>Hattel, Brian C</creator><creator>Aeby, Sebastien</creator><creator>Kebbi-Beghdadi, Carole</creator><creator>Gilbert, Benoit</creator><creator>Studer, Olivia</creator><creator>Norris, Jill M</creator><creator>Nolers, V Michael</creator><creator>Demoruelle, M Kristen</creator><creator>Feser, Marie L</creator><creator>Moss, Laura Kay</creator><creator>Courvoisier, Delphine S</creator><creator>Lauper, Kim</creator><creator>Deane, Kevin D</creator><creator>Greub, Gilbert</creator><creator>Finckh, Axel</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1956-2607</orcidid><orcidid>https://orcid.org/0000-0002-0291-8865</orcidid><orcidid>https://orcid.org/0000-0002-4315-9009</orcidid><orcidid>https://orcid.org/0000-0003-2211-4861</orcidid></search><sort><creationdate>20250101</creationdate><title>A potential role for chlamydial infection in rheumatoid arthritis development</title><author>Lamacchia, Celine ; Aymon, Romain ; Hattel, Brian C ; Aeby, Sebastien ; Kebbi-Beghdadi, Carole ; Gilbert, Benoit ; Studer, Olivia ; Norris, Jill M ; Nolers, V Michael ; Demoruelle, M Kristen ; Feser, Marie L ; Moss, Laura Kay ; Courvoisier, Delphine S ; Lauper, Kim ; Deane, Kevin D ; Greub, Gilbert ; Finckh, Axel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c288t-e2a8a28c0b47d1bbb0f637a379d346d06a0594218c1db2785eb06026c21ab73d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Clinical Science</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lamacchia, Celine</creatorcontrib><creatorcontrib>Aymon, Romain</creatorcontrib><creatorcontrib>Hattel, Brian C</creatorcontrib><creatorcontrib>Aeby, Sebastien</creatorcontrib><creatorcontrib>Kebbi-Beghdadi, Carole</creatorcontrib><creatorcontrib>Gilbert, Benoit</creatorcontrib><creatorcontrib>Studer, Olivia</creatorcontrib><creatorcontrib>Norris, Jill M</creatorcontrib><creatorcontrib>Nolers, V Michael</creatorcontrib><creatorcontrib>Demoruelle, M Kristen</creatorcontrib><creatorcontrib>Feser, Marie L</creatorcontrib><creatorcontrib>Moss, Laura Kay</creatorcontrib><creatorcontrib>Courvoisier, Delphine S</creatorcontrib><creatorcontrib>Lauper, Kim</creatorcontrib><creatorcontrib>Deane, Kevin D</creatorcontrib><creatorcontrib>Greub, Gilbert</creatorcontrib><creatorcontrib>Finckh, Axel</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Rheumatology (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lamacchia, Celine</au><au>Aymon, Romain</au><au>Hattel, Brian C</au><au>Aeby, Sebastien</au><au>Kebbi-Beghdadi, Carole</au><au>Gilbert, Benoit</au><au>Studer, Olivia</au><au>Norris, Jill M</au><au>Nolers, V Michael</au><au>Demoruelle, M Kristen</au><au>Feser, Marie L</au><au>Moss, Laura Kay</au><au>Courvoisier, Delphine S</au><au>Lauper, Kim</au><au>Deane, Kevin D</au><au>Greub, Gilbert</au><au>Finckh, Axel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A potential role for chlamydial infection in rheumatoid arthritis development</atitle><jtitle>Rheumatology (Oxford, England)</jtitle><addtitle>Rheumatology (Oxford)</addtitle><date>2025-01-01</date><risdate>2025</risdate><volume>64</volume><issue>1</issue><spage>252</spage><epage>260</epage><pages>252-260</pages><issn>1462-0324</issn><issn>1462-0332</issn><eissn>1462-0332</eissn><abstract>To assess the relationship between self-reported and serological evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA development.
This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a questionnaire on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA autoimmunity, RA-associated symptoms and RA autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against the major outer membrane protein of Chlamydia trachomatis. We replicated our analysis in an independent USA-based RA-FDR cohort.
Among 1231 RA-FDRs, 168 (13.6%) developed RA autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA autoimmunity compared with controls (17.9% vs 9.8%, odds ratio [OR] = 2.00; 95% CI: 1.27, 3.09; P < 0.01). This association remained significant after adjustments (OR = 1.91; 95% CI: 1.20, 2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA autoimmunity (OR = 3.05; 95% CI: 1.10, 8.46; P = 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity.
Self-reported chlamydial infections are associated with elevated RA autoimmunity in at-risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies, but is consistent with a role of mucosal origin of RA-related autoimmunity.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>38092030</pmid><doi>10.1093/rheumatology/kead682</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1956-2607</orcidid><orcidid>https://orcid.org/0000-0002-0291-8865</orcidid><orcidid>https://orcid.org/0000-0002-4315-9009</orcidid><orcidid>https://orcid.org/0000-0003-2211-4861</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current) |
| subjects | Clinical Science |
| title | A potential role for chlamydial infection in rheumatoid arthritis development |
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