BackgroundIn the pathogenesis of SLE an important place is given to immune mechanisms with many uncertain aspects. Adenosine deaminase (ADA), 5-nucleotidase (5-NT), adenosine kinase (ADK) and xanthine oxidase (XO) are the main enzymes of adenine branch of purine metabolism (PM), the activity of which is closely related to the immunological processes in the body. The role of antibodies to enzymes PM in systemic lupus erythematosus (SLE) is not defined and poorly studied.ObjectivesThe purpose of our work was to study antibodies to enzymes of adenine branch of PM in SLE patients and to detect correlations between studied antibodies and clinical and laboratory indices of pathological process.Methods30 healthy individuals aged 18 to 40 years (20 women and 10 men) and 60 SLE patients aged 22 to 58 years (55 women and 5 men) were included into the research. The diagnosis of SLE was verified using the ACR criteria of the 1997. The object of research was blood serum. IgG antibodies to ADA (anti-ADA), 5-NT (anti-5NT), ADC (anti-ADC) and XO (anti-XO) were determined in the method developed by us for indirect ELISA-assay using an immobilized form of the correlative enzyme as antigen matrix. Positive results were considered greater than 2 standard deviations of figures obtained during the examination of healthy persons (0.106 Unit for anti-ADA; 0.1 Unit for anti-5NT; 0.47 Unit for anti-ADC; 0.097 U for the anti-XO). The results were expressed as mean ± σ, differences were considered significant when p<0.05. Person correlation coefficient (r) was also used.ResultsAccording to the results of the research the number of SLE patients with elevated levels of anti-ADA was 51.6%, anti-5NT - 41.7%, anti-ADK - 46,7%, the anti-XO - 53.3%. Comparison between the positive and negative for the presence of anti-ADA groups of patients with SLE showed a statistically significant increase in the detection rate of chronic headaches (p=0.01), lymphopenia (p=0.025) and the definition of increased values of antibodies to phospholipids (p=0.014).Comparison between the positive and negative for the presence of blood serum anti-5NT groups of SLE patients showed an increase in the frequency of kidney damage (p=0.031) and vessels (p=0.053). Analysis of anti-5NT in relation to laboratory data allowed to identify a number of statistically significant correlations: with proteinuria (r=0,27; p=0,039), leukocyturia (r=0,35; p=0,012) and red blood cell (r=0,29; p=0,026). These data allow us to consider the anti-5NT as an additional indicator of lupus nephropathy.Among patients with the presence of anti-ADK a significant number of patients with vascular disease (p=0,023) was revealed. A bit more often, but not statistically significant, patients with the presence of anti-ADC pulmonary injury (p=0,113) and the autonomic nervous system (p=0,124) were observed.Comparison between the positive and negative for the presence of anti-CA groups of patients with SLE demonstrated a statistically significant increase in the frequency of signs of kidney (p=0.032) and blood...

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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 ...

BackgroundPurine nucleoside phosphorylase (PNP, EC 2.4.2.1) plays a leading role in the assimilation of nucleosides and nucleotides by the cell, as well as in maintaining the immune status of the organism. Patients with PNP deficiency are highly susceptible to various infections, in view of the fact that the decreased activity of PNP is closely related to the insufficiency of cellular immunity.ObjectivesStudy of the possibility of using the level antibodies to purine nucleoside phosphorylase as an additional marker of infectious complications in patients with systemic lupus erythematosus (SLE).MethodsThe study included 60 patients with SLE (women – 91.7%, mean age 36.32±15.27 years, average duration of the disease 7.96±7.35 years) with different clinical manifestations (SLEDAI activity 8.93±5,74, ECLAM activity 5.30±2.79, damage index SLICC/ACR 1.95±1.71). Antibodies to PNP (anti-PNP) were determined in our indirect ELISA test using the immobilised form of the enzyme as an antigenic matrix.The presence of infectious complications in SLE patients was assessed by characteristic clinical manifestations and was considered to be confirmed when the causative agent was recognised and/or the serological analyses are positive. Infections were diagnosed in 38.3% of patients, the most frequent localization was the urinary system (n=12; 52.2%) and female genitalia (n=5; 21.7%).ResultsIn the presence anti-PNP in the blood serum of patients with SLE we have often noted infectious complications (p=0.025, criterion χ2) and less often lung damage (p=0.17) (when compared with a group of patients with SLE seronegative for the presence of anti-PNP).Statistically significant differences (Mann-Whitney U-criterion) were detected only for pyuria (p<0.0005), C-reactive protein level (p=0.048) and the number of ceruloplasmin (p=0.008), while comparing the groups of SLE patients with the presence of infectious complications and without it; differences in the level of antibodies to CP (p=0.052) did not reach statistical significance. Other clinical and laboratory parameters do not have statistically significant differences between the two sessions. This fact complicates the recognition and differential diagnosis of infectious complications in SLE significantly.The analysis of the characteristic curve of antibodies to PNP in the diagnosis of infectious pathology in SLE shows limited possibilities for using this parameter. The square under the curve was 0.687 (95% confidence interval 0.523–0.804, p=0.008), the separation point was 0.386 U/ml with a sensitivity of 55% and a specificity of 83%.Taking into account that the typical clinical manifestations of infection with SLE can be erased as a result of the actual activity of SLE, and due to the use of immunosuppressive drugs, timely diagnosis and treatment become especially relevant. This study indicates the possibility of using the level of antibodies to PNP as an additional marker of infection, but the balance between specificity and sensitivity of this test does not allow to recommend it as ...