Background Knee osteoarthritis (kOA) results, at least in part, from overloading and inflammation leading to cartilage degradation. Inflammatory mediators such as bradykinin, histamine, prostaglandins, lactic acid, substance P, and calcitonin generelated peptide are released into the joint. Innate immune system activation, best documented in responses to pathogens, likely plays a role in induction of inflammatory mediators in kOA. Angiotensin-converting enzyme (ACE) plays an important role in a number of inflammatory and immune related disorders.
Objectives The aim of our work was to study the expression of natural antibodies against ACE (ACE-NA) in the peripheral blood sera of kOA patients and found a correlation between serum ACE-NA level and other markers.
Methods Sera were obtained from 57 patients with primary kOA fulfilling the American College of Rheumatology criteria and 57 ethnically matched healthy controls. All kOA patients had involvement of the knee joint with typical radiographic changes graded Kellgren & Lawrence classification. The presence of ACE-NA was examined by a novel ELISA. Affinity chromatography yielded ACE-NA (revealed upon Ion-exchange Chromatography on QAE Sephadex) from both kOA patients and healthy individuals. Expression of cytokines was measured by Bio-Plex Human Cytokine Assay (Bio-Rad Inc, Hercules, CA, USA).
Results ACE antibodies (IgM, IgG, IgA), reacting with ACE tested, were present in the sera of kOA patients as well as in the sera of normal individuals. Affinity chromatography yielded three (IgM, IgG, IgA) isotypes of ACE-specific NA from the both kOA patients and healthy individuals. Purified ACE-NA displayed the expected characteristics and was functionally fully active. No statistically significant differences were found between ACE-IgG and ACE-IgA for kOA patients and healthy individuals. The level of ACE-IgM in the sera from the kOA patients was significantly higher than those from the control group (P<0.005). ACE-IgM was expressed at higher levels in kOA than in other OA. No correlation was found between serum ACE-IgM level and patient’s age and body mass index. There was a positive correlation between serum ACE-IgM level and expression of pain-associated molecules such as inducible nitric oxide synthase (r=0.652; P<0.01), IL-6 (r=0.815; P<0.05) and proinflammatory cytokine as such IL-1 (r=0.789; P<0.01).
Conclusions We first identified ACE-NA in the sera of kOA patients. The ACE-IgM test gives significant information about kOA patients. Serum ACE-IgM is a good discriminator between kOA patients versus patients with other OA and healthy people. Serum ACE-IgM level may help to classify OA patients. We shown that their could be used a specific marker for diagnosis and prognosis of primary kOA. Renewed interest in ACE antibodies opens up a new area for kOA diagnostics and therapeutics.
Shehab DK. Prevalence of ACE gene insertion-deletion polymorphism in patients with prymary knee osteoarthritis. Clin Exp Rheum 2008, 26:305-10
Disclosure of Interest Y. Savitskaya Grant/Research support from: FONSEC SSA/IMSS/ISSSTE/CONACyT SALUD-2010-C01, C. Duarte: None Declared, N. Marin: None Declared, R. Tellez: None Declared, C. Ibarra: None Declared.