Background Today’s leading laboratory researchers, pharmacy and biotech decision-makers, technology companies and clinicians are focusing on the uses of biomarkers in the field of osteoarthritis research. In kOA disease, pathogenic pain-associated molecules are used for development of diagnostic criteria, monitoring of disease activity, and prognosis. As such, the body has many pain messengers, receptors and neural pathways to sense that information. Analysis of circulating immune complexes (CICs) produced during an immune response may be useful in elucidating some aspects of kOA process.
Objectives To investigate the presence of immune complexes containing pain-associated molecules such as interleukin 6 (IL-6), interleukin 18 (IL-18), angiotensin-converting enzyme (ACE), prostaglandin E2 (PGE2) in the peripheral blood sera of kOA patients and to evaluate their potential as markers of kOA pathogenesis.
Methods Circulating biomarker-Ig immune complexes were measured in serum samples from 54 patients with kOA and from 54 healthy controls using a novel ELISA (INR, Mexico). kOA severity as defined by increasing Kellgren & Lawrence (KL) grade. Pain was measured using a visual analogue scale (VAS, 0-100 mm). kOA biopsies were obtained at arthroscopy.
Results We applied our strategy to the analysis of CICs in kOA patients and healthy controls. Our technique for CICs analysis uses routine clinical samples, simple protocols, and widely available equipment. CICs containing PGE2 and IL-18 were found in the serum of 81% and 65% of kOA patients. Serum PGE2-IgG and IL-18-IgG are significantly higher in the kOA group than those in the control group (P<0.01). A significant positive correlation was noted between their expressions (r=0.863, P<0.01). No correlation between the serum PGE2-IgG and IL-6-IgG was found. Deficiency in the sera ACE-IgM predisposes the expression of high affinity PGE2-IgG in kOA patients. There was a negative correlation between serum PGE2-IgG and ACE-IgM in kOA patients (r=-0.58, P<0.05).
Conclusions Blood still represents an ideal clinical source of markers because of its known role in reflecting systemic changes associated with disease. Improved analytical methods are required to accommodate the analysis of large numbers of samples for biological and epidemiological monitoring. Our method may be generally applicable to the study of the relationship between CICs and kOA diseases. The ICs in the serum of a majority of the OA patients contained PGE2 or ACE, and these ICs may have potential as alternative biomarkers. The role of ACE-IgM and PGE2-IgG in the modulation of the immune response, pain and inflammation has been regarded as important.
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Disclosure of Interest Y. Savitskaya Grant/Research support from: FONSEC SSA/IMSS/ISSSTE/CONACyT SALUD-2010-C01, C. Duarte: None Declared, R. Tellez: None Declared, N. Marin: None Declared, E. Vilallobos: None Declared, A. Almazan: None Declared, C. Ibarra: None Declared