AB0479 The role of antibodies to xanthine oxidase and adenosine deaminase in the development of anti-phospholipid syndrome in patients with systemic lupus erythematosus

Abstract

ObjectivesThe aim of the research was to study the processes of formation of antibodies to the enzyme purine metabolism (PM) - xanthine oxidase (XO) and adenosine deaminase (ADA) - in patients with systemic lupus erythematosus (SLE) with laboratory indicants of secondary antiphospholipid syndrome (APS).Methods30 healthy people and 60 SLE patients with different clinical manifestations were included in this research. Antibodies to the investigated enzymes were determined in the procedure of an indirect ELISA-test using immobilized form of the corresponding enzyme as antigen array (We have developed this technique). The results of the detection of antibodies to the XO (anti-XO), antibodies to ADA (anti-ADA) and antibodies to the ADC (anti-ADC) were recorded on a spectrophotometer at a wavelength of 450 nm. b2-glycoprotein-I-dependent (b2GP-I) to the phospholipid antibodies (aPL) class IgM and IgG were determined by using a commercial test kit “Anti-Phospholipid Screen IgG/IgM” (Orgentec). The levels of IgG aPL/IgM did not exceed 10 GPL/MPL-U/ml in the group of healthy individuals.ResultsAccording to the survey the number of SLE patients with elevated levels of anti-ADA was 51.6%, the anti-XO - 53.3%. There has been a number of statistically significant correlations between the presence of anti-XO with clinical and laboratory parameters: the level of circulating immune complexes (r=0.297, p=0.024), with a hemoglobin level (r= -0.286, p=0.042), the number of lymphocytes (r= -0.29, p=0.033), and platelets (r= -0,308, p=0.028). In 25 (41.7%) patients with SLE aPL IgG class were detected, in 19 (31.7%) - aPL IgM were detected. As a result of multivariate dispersive analysis leading role of aPL in the development of APS has been established (F=52,5, p<0,001).In positive for the presence of anti-ADA patients with SLE aPL IgG class (but not aPL class IgM) were detected more frequently and at higher titer than in SLE patients, without this type of antibodies (p=0.029). Joint detection of anti-ADA and aPL in patients with SLE manifestations was associated with cytopenia (p=0.019, Fisher's exact test). It was also noted that elevated levels of anti-XO were significantly more frequently detected in patients which were also positive for the presence of aPL IgG class (p=0.036) and aPL IgM class (p=0.044). Comparison of the groups of patients with SLE, the positive and negative for the presence of anti-XO, demonstrated a statistically significant increase in the frequency of signs of vasculopathy (chi-square=4.4, p=0.042).Considering a direct link between the level of anti-XO and the level of the CIC we can assume that the anti-XO in the composition of the CIC have some impact on the transformation of “xanthine oxidase ↔ xanthine dehydrogenase” in the direction of increasing the formation of XO and, as a consequence, a significant increase of generation of superoxide radicals, release of calcium ions into the extracellular space, and, in addition, platelet aggregation and increased blood viscosity.ConclusionsAntibodies to enzymes ...