Serum sRAGE, sRANKL and osteoprotegerin in subgroups of rheumatoid arthritis patients: biomarkers associated with iron and disease status

Abstract

Soluble receptors are important for the balance between ligands and their membrane receptors. Changes in the expression of soluble receptors are associated with human diseases. The aim of this study was to determine the serum levels of sRAGE, sRANKL and OPG in subgroups of rheumatoid arthritis (RA) patients according to the level of CRP and to assess the relationship of these parameters with markers of iron and disease status. The study involved 114 RA patients. The levels of sRAGE, sRANKL and OPG were higher in the subgroup with increased CRP level compared to the subgroup with normal CRP. sRAGE showed a significant positive correlation with sTfR (r = 0.435, p < 0.0001), prohepcidin (r = 0.232, p = 0.04), sRANKL (r = 0.636, p < 0.0001), RF (r = 0.363, p < 0.002), and antiCCP antibodies (r = 0.429, p = 0.003) in the subgroup with normal CRP. Serum sRANKL was positively associated with sRAGE (r = 0.636, p < 0.0001), sTfR (r = 0.513, p < 0.0001), CRP (r = 0.223, p = 0.048), DAS28 (r = 0.269, p = 0.016), RF (r = 0.390, p = 0.001) and antiCCP antibodies (r = 0.445, p = 0.002) also in the subgroup with normal CRP. Serum OPG was positively correlated with ferritin in the subgroup with normal CRP. The association of sRAGE, sRANKL and OPG with markers of iron and disease status in RA suggests a relationship between inflammatory state, osteoclast activation and impaired iron and immune status. Therefore, sRAGE, sRANKL and OPG can be useful markers for the assessment of early pathological changes in RA and can also assist in monitoring of the therapy.

Keywords:

• sRAGE
• sRANKL
• osteoprotegerin
• rheumatoid arthritis
• iron metabolism
• inflammation

Acknowledgments

The authors would like to thank Prof. Ana Maneva, PhD, DSc (Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv) for her assistance and support in the preparation of the manuscript.

Authors’ contributions

Conceptualization, G.D. and K.S.; methodology and investigation, G.D., K.S. and T.S.; sample collection, G.D. and K.S.; sample preparation G.D., K.S. and T.S.; data analysis and interpretation, G.D., K.S. and T.S.; writing-original draft preparation, G.D. and K.S.; writing-review and editing, K.S. and T.S. All authors have read and agreed to the final version of the manuscript.

Disclosure statement

The authors report no conflict of interest.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, GD. The data are not publicly available due to their containing information that could compromise the privacy of research participants.

Additional information

Funding

This work was supported by an Intrauniversity research project number HO-11/2013 of the Medical University of Plovdiv and by the Bulgarian Ministry of Education and Science under the National Program ‘Young Scientists and Postdoctoral Students-2’.