S13.11 CIRCULATING NATURAL IGA ANTIBODIES AGAINST ANGIOGENIN AND RISK OF POST-SURGICAL JOINT PROSTHESIS INFECTION.

Abstract

Joint prosthesis infection after post-surgical intervention is an emergency. Infection development and progression are inherently dependent on the process of angiogenesis. Many immune disorders are associated with circulating natural antibodies, which bind self-protein as angiogenin (ANG). Biomarkers as anti-ANG IgA show a predisposition for infection development and must be attended by the strategies for therapeutic interventions.

To determine the relationship between the serum levels of anti-ANG IgA and risk of post-surgical joint prosthesis infection (JPI).

We have developed a ELISA, in which ANG coupled to high-molecular weight matrix (polyphenylacrylate) was coated on microtiter plates. Human serum samples were incubated in the plates, after which bound anti-ANG IgA was detected with mouse anti-human IgA-HRP. The optimal sensitivity and specificity of the assay was 91% and 84%. The specificity of ELISA was confirmed by the immunoprecipitation/immunoblotting control experiments. Serum levels of anti-ANG IgA in a cohort of healthy donors differed by more than a hundred-fold, whereas the fluctuation of anti-ANG IgA levels in individuals over time was small (coefficient of variation 6%). The study began in October 2005 and finish December 2008. For first study samples were collected from Department of Hip and Knee Articular Reconstruction. In this period we have operated 1290 patients with joint prostheses implanted. A second study examined specimens collected in Department of Bone Infections from 119 patients with JPI. In both studies, detection of anti-ANG IgA in sera by ELISA. JPI was defined as acute clinical sings of infection during the first 3 months after the placement of the prosthesis. Serum samples were obtained from 500 healthy adults.

IgA antibodies, reacting with ANG tested, were present in the sera of all patients as well as in the sera of normal individuals. Serum levels of anti-ANG IgA are significantly low in 19.1% patients with pre-surgical total joint replacement than in healthy individuals (m±SD: 385±101 versus 121±98; P< 0.001). Very low serum levels of anti-ANG IgA, as occur in primary immunodeficiency syndromes, are associated with significantly increased risk of infections (r=0.85; P< 0.005). Increases in serum anti-ANG IgA to normal/higher levels in patients before surgery associated with good response after gammaglobulin replacement therapy (m±SD: 385±101 versus 587±189; P< 0.001).Risk of JPI was dependently associated with secretory anti-ANG IgA antibody responses. Very low the expression of anti-ANG IgA in sera seem to be potentially useful as angiogenic biomarkers of risk JPI.