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Plasma soluble IL-6 receptor concentration in rheumatoid arthritis: associations with the rs8192284 IL6R polymorphism and with disease activity

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Abstract

Soluble interleukin-6 receptor α subunit (sIL-6R) is primarily generated by shedding of the membrane-bound form. This process is influenced by the single nucleotide polymorphism rs8192284 (A > C) resulting in an aspartic acid to alanine substitution (D358A) at the proteolytic cleavage site. The aim of this study was to determine whether plasma levels of sIL6R are influenced by the rs8192284 polymorphism in patients with rheumatoid arthritis and to assess the association between plasma sIL-6R levels and disease activity as reflected by anti-CCP status. Thirty-nine patients were randomly selected from a cohort of patients with RA of Spanish descent. Plasma sIL-6R concentrations were measured using sandwich ELISA. Genotyping of the rs8192284 (A > C) polymorphism was done using a Fast Real-Time PCR System. DAS 28 scores were used to assess disease activity. Plasma sIL-6R levels were positively associated with the number of C alleles (AA: 35.27 (3.50) ng/ml, AC: 45.50 (4.58) ng/ml, CC: 52.55 (3.18) ng/ml, P = 0.0001). DAS28 and plasma sIL-6R levels were positively associated in the anti-CCP-positive subgroup (r 2 = 0.45, P = 0.0336) and negatively associated in the anti-CCP-negative subgroup (r 2 = −0.45, P = 0.0825). No association between anti-CCP status and sIL-6R level was found. Our findings show that the rs8192284 polymorphism is operative in patients with RA. The presence of anti-CCP antibodies determines the relationship between sIL-6R concentration and disease activity.

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Acknowledgments

This work was supported by a research grant from Roche Farma S.A. It was also partially supported by the RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII).

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Authors and Affiliations

  1. Rheumatology Service, Hospital Clinico San Carlos, C/Profesor Martín Lagos s/n, 28040, Madrid, Spain

    Luis Rodríguez-Rodríguez, José Ramón Lamas, Pilar Tornero-Esteban, Lydia Abasolo, Juan Angel Jover & Benjamín Fernández-Gutiérrez

  2. Immunology Service, Hospital Clinico San Carlos, 28040, Madrid, Spain

    Jezabel Varadé, Emilio Gomez de la Concha & Elena Urcelay

  3. Department of Cardiovascular Epidemiology and Population Genetics, CNIC, 28029, Madrid, Spain

    Pedro López-Romero

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  1. Luis Rodríguez-Rodríguez
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  2. José Ramón Lamas
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  4. Pedro López-Romero
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  10. Benjamín Fernández-Gutiérrez
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Correspondence to Benjamín Fernández-Gutiérrez.

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Luis Rodríguez-Rodríguez and José Ramón Lamas are contributed equally to this paper.

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Rodríguez-Rodríguez, L., Lamas, J.R., Varadé, J. et al. Plasma soluble IL-6 receptor concentration in rheumatoid arthritis: associations with the rs8192284 IL6R polymorphism and with disease activity. Rheumatol Int 31, 409–413 (2011). https://doi.org/10.1007/s00296-010-1593-0

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