Martinsson Klara, Di Matteo Andrea, Öhman Carina, Johansson Anders, Svärd Anna, Mankia Kulveer, Emery Paul, Kastbom Alf
Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Leeds Musculoskeletal Biomedical Research Unit, LTHT and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom.
Front Med (Lausanne). 2023 Aug 3;10:1176165. doi: 10.3389/fmed.2023.1176165. eCollection 2023.
Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is (.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA.
Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls.
Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04-4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60-1.65).
Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.
牙周炎及相关细菌与类风湿关节炎（RA）的发病有关。一种被认为的病原体是（.），它表达白细胞毒素A（LtxA），可使人类蛋白质瓜氨酸化，这可能是抗瓜氨酸化蛋白抗体（ACPA）产生的触发因素。在本研究中，我们试图确定有患RA风险的患者体内是否存在针对LtxA的抗体。
对两个有症状的高危患者前瞻性观察队列（一个瑞典队列和一个英国队列）进行了研究。通过基于细胞的中和试验分析基线血清中的抗LtxA抗体，并与100名瑞典献血者作为对照进行比较。
患者和献血者之间血清抗LtxA水平或阳性率无差异。在英国队列中，与ACPA阴性的关节痛患者相比，ACPA阳性的关节痛患者中抗LtxA更为普遍（24%对13%，<0.0001）。在瑞典高危队列中，抗LtxA阳性患者进展为关节炎的风险增加（风险比（HR）2.10，95%CI 1.04 - 4.20），但在英国高危队列中未得到证实（HR 0.99，CI 0.60 - 1.65）。
在RA诊断前血清抗LtxA未升高，且疾病进展和ACPA水平的关联在不同人群中存在差异。在未来与牙周炎相关的RA研究中应探索口腔微生物群的其他特征。
