Journal of Molecular Biomarkers & Diagnosis

Identification of Circulating Natural Antibodies against Endogenous Mediators in the Peripheral Blood Sera of Patients with Osteoarthritis of the Knee: A New Diagnostic Frontier

Abstract

Yulia A Savitskaya, Carolina Duarte, Norma Marín, René Téllez, Alfonso Alfaro and Clemente Ibarra

Introduction: The presence of NA against EM regarding specificity and have gained increasing attention in proteome analysis for diagnosis, developing, monitoring and effective treatment of osteoarthritis of the knee (kOA). An understanding of the various regulatory systems controlling blood vessel growth, inflammation and pain in the join should lead to help explain kOA disease progression. To investigate the specific presence of NA (IgM, IgG, IgA) against EM (BK, AII, VEGF, bFGF) in the sera of kOA patients and control and to correlate this with process of joint destruction.

Methods: In this study novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive ELISA method to directly detect immune complexes (NA-EM) in humans. Following this procedure, we examined variations in the levels of natural antibodies recognized a panel of self-antigens in the sera from healthy individuals and kOA patients. Blood samples were obtained from 250 patients with symptomatic kOA and 250 ages, sex-matched healthy individuals.

Results: NA against EM was detected with novel ELISA assay in the sera of kOA patients as well as in the sera of control. At time of inclusion kOA patients (100%) had significantly higher BK-IgG levels relative to normal sera. The over expression BK-IgG were positively associated with destructive changes (KL>4; r=0.75; p<0.005). KOA patients in whom KL scores progress rapidly tend to have higher BK-IgG levels at all time point. Serum BK-IgG over expression in kOA patients were positively associated with destructive changes (KL>4; r=0.75; p<0.005). Elevated BK-IgG was significantly correlated with VAS (r=0.85; p<0.0001) and loss of functions (r=0.69; p<0.0003) in kOA patients. Affinity chromatography yielded EM-specific NA from the sera of healthy individuals and kOA patients.

Conclusions: We showed that EM represents a group of novel self-antigens which are targeted by NA from kOA patients. Circulating BK-IgG in the sera has been proposed as a sensitive and specific marker of diagnosing kOA at early stages of the disease. Our results have potential applications for controlling unwanted angiogenesis, inflammation, pain and future response to therapy in kOA patients.