Comparative Analysis of Serum Proteins in Relation to Rheumatoid Arthritis and Chronic Periodontitis

• Localización: Journal of periodontology, ISSN 0022-3492, Nº. 1, 2014, págs. 103-112
• Idioma: inglés
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• Resumen

  • Background: Rheumatoid arthritis (RA) and chronic periodontitis (CP) are chronic inflammatory conditions and share many pathologic features. The common molecular pathogenesis of the two inflammatory diseases is unclear. The aim of the present study is to evaluate serum protein profiles specific for patients with RA and CP by a comprehensive proteomic analysis.

    Methods: The study participants were: 10 patients with RA, 10 patients with CP, 10 patients with RA and CP, and 10 healthy controls. All groups were balanced for age, sex, and smoking status. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant differences in abundance among the four groups were determined with computer image analysis and identified with mass spectrometry and protein databases.

    Results: A total of 1,694 protein spots were obtained in sera of the four groups. Seven spots were significantly different in abundance among the four groups. Of these, three spots (complement component 3, complement factor H, and ceruloplasmin) were significantly different in the RA+CP group compared with the other three groups (P <0.05). The similar profiles of complement component 3, complement factor H, and ceruloplasmin were observed by enzyme-linked immunosorbent assay.

    Conclusion: These results suggest that patients with RA and CP may exhibit three serum proteins with different abundance compared with healthy controls and patients with RA only or CP only.

    Similarities have been suggested in the clinical and pathologic features of rheumatoid arthritis (RA) and chronic periodontitis (CP).1-3 Both diseases represent chronic destructive inflammatory diseases characterized by accumulation and persistence of inflammatory infiltrates in local lesions. Patients with RA exhibiting synovitis and breakdown of the joint were more likely to have CP,4-9 whereas patients with moderate-to-severe CP had a higher prevalence of RA than those without CP.9 These observations imply that certain features of the inflammatory response are common to both diseases, which might be underpinned by biologic causal and non-causal pathways.3 As a causal pathway, there is evidence to suggest that CP could contribute to the etiology of RA. It has been reported that increased levels of antibodies to periodontopathic bacteria were detected in sera and synovial tissues of patients with RA.10-13 Serum levels of immunoglobulin G (IgG) antibodies to Porphyromonas gingivalis were correlated with those of anticyclic citrullinated peptide,11,12 suggesting that serum protein citrullination via peptidylarginine deiminase of P. gingivalis drives RA responses. Furthermore, the presence of RA might predispose individuals to CP. Studies with experimental arthritis indicated that increased levels of serum cytokines and matrix metalloproteinases led to periodontal tissue breakdown.14,15 As a non-causal pathway, similarities have been reported in serum cytokine and gene expression profiles between the patients with RA and those with CP.7,16-19 The pathogenesis of both diseases is also characterized by increased levels of serum matrix metalloproteinases, reactive oxygen species, lipid mediators, and neutrophil-associated enzymes.1-3 It has further been proposed that polymorphisms relating to genes encoding inflammatory cytokines might confer susceptibility to RA and CP.20-22 These findings suggest the importance of using a serum biomarker to predict individuals at high risk for developing RA and CP. However, the common molecular pathogenesis of the two diseases has not been studied. Therefore, it is necessary to perform a comprehensive proteomic study that allows global assessment of changes in serum protein/peptide abundance under physiologic versus pathologic conditions.23,24 Some studies have performed proteomic analysis of saliva and gingival crevicular fluid from patients with CP.25-27 The aim of the present study is to evaluate the serum protein profiles specific for patients with RA and CP, by comparison with patients with RA only and CP only and healthy controls, with two-dimensional gel electrophoresis and mass spectrometry of the proteins.