Are the Soluble Receptors sRAGE, sRANKL, and Osteoprotegerin Associated with Anemia in Rheumatoid Arthritis?

Abstract

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with articular and systemic manifestations, and one of the most common is anemia. This study aims to investigate whether the levels of the soluble receptors sRAGE, sRANKL, and OPG are affected by the distribution of RA patients in subgroups according to soluble transferrin receptor/log ferritin (sTfR-F index) and hemoglobin (Hb) levels and to examine their correlation with indicators of iron metabolism, disease activity, and autoimmune and inflammatory changes. The levels of sRANKL and sRAGE were significantly higher in the subgroup of anemia of chronic disease combined with iron deficiency anemia (ACD/IDA) compared to the ACD group: p < 0.0001 and p < 0.0001. The level of OPG tended to decrease in ACD/IDA (p = 0.053). sRAGE was positively correlated with prohepcidin, RF and anti-CCP antibodies, sRANKL, CRP, and IL-6 only in the ACD group. A negative correlation was found between sRAGE, sRANKL, and serum iron only in the ACD/IDA group. sRANKL was positively correlated with OPG, prohepcidin, CRP, IL-6, RF, anti-CCP antibodies, and DAS28 only in the ACD group. Positive correlations were observed between OPG and ferritin, sTfR, CRP, IL-6, RF, and DAS28, and a negative correlation was observed with serum iron only in the ACD group. Therefore, the investigated soluble receptors may serve as reliable biomarkers involved in the pathogenesis of RA and may contribute to the identification of patients at risk of developing combined anemia.