Antibodies to Porphyromonas gingivalis Are Associated with Anticitrullinated Protein Antibodies in Patients with Rheumatoid Arthritis and Their Relatives
Antibodies to Porphyromonas gingivalis Are Associated with Anticitrullinated Protein Antibodies in Patients with Rheumatoid Arthritis and Their Relatives
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DOI：
10.3899/jrheum.091323
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发表时间：
2010-06-01
影响因子：
3.9
通讯作者：
El-Gabalawy, Hani S.
中科院分区：
文献类型：
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作者：
Hitchon, Carol A.;Chandad, Fatiha;El-Gabalawy, Hani S.
Objective.抗瓜氨酸蛋白抗体（ACPA）对类风湿性关节炎（RA）具有相对特异性，并可早于疾病。口腔病原体牙龈卟啉单胞菌可能在破坏对瓜氨酸化抗原的免疫耐受性方面发挥作用。我们研究了一组RA患者及其亲属，寻找抗牙龈卟啉单胞菌抗体和ACPA之间的联系。研究了来自北美土著（NAN）人群的RA患者（n = 82）及其亲属（n = 205），沿着有47名NAN和60名非NAN对照。用散射比浊法和ELISA法检测IgM和伊加类风湿因子（RF）。通过ELISA检测第二代抗环瓜氨酸肽（抗CCP 2）同种型和IgG抗牙龈卟啉单胞菌脂多糖。HLA-DRB 1分型采用测序法。口腔卫生和吸烟习惯通过问卷进行评估。RA患者及其亲属的自身抗体频率：ACPA分别为91%和19%; IgM RF为82%和17%;伊加RF为48%和22%。RA患者的抗牙龈卟啉单胞菌水平高于亲属和对照组（p = 0.005），ACPA阳性RA患者的抗牙龈卟啉单胞菌水平高于ACPA阴性RA患者（p = 0.04）和亲属（p < 0.001），但RF阳性和RF阴性患者和亲属的抗牙龈卟啉单胞菌水平相当。口腔卫生不良和吸烟是普遍存在的，但与自身抗体没有明确的联系。具有2个共享表位等位基因的亲属更可能是ACPA阳性（OR 2.5，p = 0.02）。在遗传易感人群NAN RA患者及其亲属中，抗牙龈卟啉单胞菌抗体与ACPA相关。这些发现表明，对牙龈卟啉单胞菌的免疫应答可能参与破坏对瓜氨酸化抗原的免疫耐受。（2010年5月1日首次发布; J Rheumol 2010;37：1105-12; doi：10.3899/jrheum.091323）
Objective. Anticitrullinated protein antibodies (ACPA) are relatively specific for rheumatoid arthritis (RA), and predate disease. The oral pathogen Porphyromonas gingivalis may play a role in breaking immune tolerance to citrullinated antigens. We studied a cohort of patients with RA and their relatives looking for associations between anti-P. gingivalis antibodies and ACPA.Methods. Patients with RA (n = 82) and their relatives (n = 205) from a North American Native (NAN) population were studied, along with 47 NAN and 60 non-NAN controls. IgM and IgA rheumatoid factor (RF) were tested by nephelometry and ELISA. Second-generation anticyclic citrullinatal peptide (anti-CCP2) isotypes and IgG anti-P. gingivalis lipopolysaccharides were tested by ELISA. HLA-DRB1 typing was performed by sequencing. Oral hygiene and smoking habits were assessed by questionnaires.Results. Autoantibody frequency in patients with RA and relatives: ACPA 91% vs 19%, respectively; IgM RF 82% vs 17%; IgA RF 48% vs 22%. Anti-P. gingivalis levels were higher in patients with RA compared to relatives and controls (p = 0.005) and higher in ACPA-positive patients with RA than in ACPA-negative patients with RA (p = 0.04) and relatives (p < 0.001), but comparable in RF-positive and RF-negative patients and relatives. Poor oral hygiene and smoking were prevalent, but with no clear association with autoantibodies. Relatives with 2 shared-epitope alleles were more likely to be ACPA-positive (OR 2.5, p = 0.02).Conclusion. In a genetically predisposed population of NAN patients with RA and their relatives, anti-P. gingivalis antibodies were associated with ACPA. These findings suggest that immune responses to P. gingivalis may be involved in breaking immune tolerance to citrullinated antigens. (First Release May 1 2010; J Rheumatol 2010;37:1105-12; doi:10.3899/jrheum.091323)