Periodontal and Serum Protein Profiles in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitor Adalimumab
- Autores: Tetsuo Kobayashi, Tomoko Yokoyama, Satoshi Ito, Daisuke Kobayashi, Akira Yamagata, Moe Okada, Ken Oofusa, Ichiei Narita, Akira Murasawa, Kiyoshi Nakazono, Hiromasa Yoshie
- Localización: Journal of periodontology, ISSN 0022-3492, Vol. 85, Nº. 11, 2014, págs. 1480-1488
- Idioma: inglés
- Enlaces
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Resumen
Background: Tumor necrosis factor (TNF)-α inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-α monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients with RA and to compare serum protein profiles before and after ADA therapy.
Methods: The study participants consisted of 20 patients with RA treated with ADA. Clinical periodontal and rheumatologic parameters and serum cytokine levels were evaluated at baseline and 3 months later. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant difference in abundance before and after ADA therapy were found and identified using mass spectrometry and protein databases.
Results: The patients showed a significant decrease in gingival index (P = 0.002), bleeding on probing (P = 0.003), probing depth (P = 0.002), disease activity score including 28 joints using C-reactive protein (P <0.001), and serum levels of TNF-α (P <0.001) and interleukin-6 (P <0.001) after ADA medication, although plaque levels were comparable. Among a total of 495 protein spots obtained, nine spots were significantly decreased in abundance at reassessment, corresponding to complement factor H, phospholipase D, serum amyloid A, complement component 4, and α-1-acid glycoprotein (P <0.01).
Conclusion: These results suggest a beneficial effect of ADA therapy on the periodontal condition of patients with RA, which might be related to differences in serum protein profiles before and after ADA therapy.
Rheumatoid arthritis (RA) and periodontitis have been suggested to share many clinical and pathologic features.1,2 Both diseases represent chronic inflammatory diseases characterized by accumulation and persistence of inflammatory infiltrates in local lesions. Patients with RA exhibiting synovitis and destruction of the joint were more likely to have periodontitis,3-5 whereas patients with moderate-to-severe periodontitis had a higher prevalence of RA than those without periodontitis.5-7 These observations imply that certain features of the inflammatory response are common to both diseases, which might be underpinned by biologic pathways.2 A similar profile of cytokines has been involved in the pathogenesis of RA and periodontitis.1,2 In particular, tumor necrosis factor (TNF)-α has been suggested as one of the most potent cytokines associated with these two inflammatory diseases.8,9 It is well recognized that TNF-α plays a central role in inflammatory reactions, including alveolar bone resorption and the loss of connective tissue attachment in periodontitis.9 It has also been documented that TNF antagonists inhibited loss of tissue attachment and bone in a model of experimental periodontitis.10,11 It was further reported that TNF-α blockade led to improvement of clinical arthritis condition in a mouse model of collagen-induced arthritis.12 These findings suggest that constitutive overproduction of TNF-α may play a pathologic role in RA and periodontitis.
Recently, TNF inhibitors have been evaluated for their efficacy on periodontal condition in patients with RA.13-17 It has been shown that treatment with infliximab (IFX), a chimeric mouse/human anti-TNF-α monoclonal antibody, proved beneficial in suppressing periodontal disease in patients with RA.13,14,16 Other studies also demonstrated an improvement of clinical periodontal condition in patients who were treated with IFX; etanercept (ETN), a recombinant fusion protein linked to human type II TNF receptor-Fc portion; or adalimumab (ADA), a fully humanized anti-TNF-α monoclonal antibody.15,17 However, there has been no study that evaluated the effect of ADA therapy alone on periodontal condition.
These three TNF inhibitors, IFX, ETN, and ADA, were shown to be comparable in effectiveness for the treatment of RA,18 but their difference in biologic effects has been suggested.19-21 ETN is able to bind TNF-α and TNF-β, whereas IFX and ADA can bind only TNF-α. It has been reported that both IFX and ADA exert complement-dependent cytotoxicity and antibody-dependent, cell-mediated cytotoxicity, as well as outside-to-inside signals through transmembrane TNF-α, whereas ETN had only antibody-dependent, cell-mediated cytotoxicity activity.19 Therefore, it is necessary to perform a comparative proteomic study that allows global assessment of changes in serum protein/peptide abundance before and after anti-TNF therapy, which might provide the molecular mechanisms by which TNF inhibitors prove effective in the treatment of RA and periodontitis. A few studies have shown a difference in serum protein profile before and after treatment with IFX and ETN.20,21 However, there is no information to date on the effects of treatment with ADA alone on serum protein profile in patients with RA.
Therefore, the aim of the present study is to assess the effects of ADA therapy on periodontal condition in patients with RA, as determined by gingival index (GI), bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL). Additionally, serum protein profiles were compared before and after ADA therapy with two-dimensional (2D) gel electrophoresis and mass spectrometry of the proteins.
