Detection of 16α-Hydroxyestrone-histone 1 Adduct as High-Affinity Antigen for Rheumatoid Arthritis Autoantibodies

Increased concentrations of 16α-hydroxyestrone (16α-OHE₁) have been observed in rheumatoid arthritis (RA), but the underlying mechanism of this remains elusive. Here we aimed to identify the role played by 16α-OHE₁ in RA. In 40 RA patients, the specificities of antibodies from the sera of these patients were checked by direct binding, inhibition ELISA, and quantitative precipitation titration. Competition ELISA was also used for the estimation of 16α-OHE₁ in the serum of different RA patients. RA IgG from a patient's sera showed strong recognition to 16α-OHE₁-H₁ (histone 1) adduct in comparison to control subjects (p < 0.001), as the formation of this adduct brings out various biochemical changes that might generate neo-epitopes, which have been well-recognized by these antibodies. The affinity of RA antibodies for 16α-OHE₁-H₁ (1.10 × 10^- 7 M) was high, as detected by the Langmuir plot. Comparing RA patients to the controls, no significant differences were detected in the level of 16α-OHE₁ or 2-hydroxyestrone/16α-OHE₁ ratio. 16α-OHE₁-H₁ might have an antigenic role and function as a high-affinity antigen for RA autoantibodies and, therefore, could be used as a biomarker for this disease.