Infectioue endocarditis (IE) is frequently associated with the use of narcotic drugs, glucocorticosteroids, and cytostatics that are metabolized in the body by enzymes of the xenobiotic detoxification system (XDS). This work was aimed at elucidating association between IE and mononucleotide polymorphisms of genes encoding XDS enzymes. 46 IE patients and 114 subjects without cardiovascular diseases (controls) underwent genotyping for polymorphic loci of cytochrome P450 1A1 gene I462V (CYP1A1), I105VandA114V gene of glutathione-S-transferase Pi1 (GSTP1) using allele-specific PCR. The study revealed association of CYP1A1 I462VandGSTP1 I105V with IE while IE proved unrelated to GSTP1 A114V polymorphism. Combination of homozygous variant I462I of the CYP1A1 gene and heterozygous variant I105V/ of the GSTP1 gene was associated with the 9-fold increase of the risk of IE in the subjects practicing intravenous druginjections or having congenital and acquired heart failure or implanted valve prostheses. These findings suggest the necessity of further studies on the role of XDS in pathogenesis of IE and other infectious diseases.
Резюме. Исследовали содержание секреторного иммуноглобулина А в сыворотке крови (ssIgA) при алкогольной болезни печени (АБП, 59 мужчин и 23 женщины) и неалкогольной жировой болезни печени (НАЖБП, 17 мужчин и 93 женщин) по сравнению с лицами без патологии печени (контроль, 43 мужчины и 73 женщины), а также возможную связь между показателем ssIgA и полиморфизмом Gln223Arg гена рецептора лептина. В работе применяли иммуноферментный анализ и аллель-специ-фическую полимеразную цепную реакцию. Обнаружено, что содержание ssIgA в среднем в группе с АБП (11,45±0,82 мг/л) было в три раза больше, чем в группе с НАЖБП (4,35±0,35 мг/л) и в группе контроля (3,60±0,29 мг/л). Концентрация ssIgА не зависела от ожирения и пола. У носителей гетеро-зиготного варианта Gln223Arg с НАЖБП концентрация ssIgА была повышена по сравнению с кон-тролем. Однако частота встречаемости аллелей 223Arg и 223Gln была практически равной во всех обследованных группах у лиц с концентрацией ssIgА выше нормы по сравнению с лицами с нормаль-ной концентрацией ssIgА. Таким образом, нами не выявлено связи полиморфизма Gln223Arg гена рецептора лептина с ssIgA. Полученные данные будут полезны при изучении генетических факторов повышенного риска развития инфекционных поражений слизистых оболочек.
Ключевые слова: сывороточный секреторный IgA, полиморфизм гена LEPR, заболевания печени
The effect of blood substitute perftoran on the content of alpha(1)- and alpha(2)-macroglobulins in the plasma and exudate was studied in rats with acute exudative inflammation. After intravenous injection of perftoran macroglobulin content increased in the plasma, but remained unchanged in the peritoneal fluid.
Insufficiency of local immunity can play an important role in pathogenesis of sepsis, including septic (acute) infectious endocarditis (IE). The paper presents data on secretory immunoglobulin A (sIgA) contents in blood serum of patients with sepsis (26 women and 32 men), acute (11 women and 23 men) and subacute (7 women and 13 men) IE, depending on localization of the infection site (angiogenic or non-angiogenic), outcome of the disease and carriage of glutathione-S-transferase P1 gene variants (GSTP1Ile105Val). A control group consisted of 25 women and 24 men without hypertension and ischemic heart disease and lacking evidence of focal and systemic infection, was examined. Laboratory studies were performed with еnzyme immunoassay and allele-specific polymerase chain reaction. We have found that, despite large individual variability of serum sIgA concentration in sepsis and infectious endocarditis, the majority of patients had a significant (on average, 4-fold) IgA increase against controls, in both men and women, especially in acute IE (a mean of 5-fold over control values). Subacute infectious endocarditis is associated with lesser sIgA in circulation than acute IE and sepsis, which may be used for early differential diagnosis of these conditions. There were no gender differences in sIgA contents. In sepsis with non-angiogenic source of infection, the sIgA levels were higher than in angiogenic infection. There was no association of sIgA level with survival (mortality), which excludes this index from predictive markers in sepsis and IE. Carriage of heterozygous GSTP1Ile105Val genotype increases the risk of sepsis and IE development, regardless of clinical course, and homozygous genotype GSTP1Ile105Ile is associated with higher contents of circulating immunoglobulin than in carriers of GSTP1Val105Val genotype. Thus, a wide range of individual variability in of circulating sIgA levels in patients with sepsis and infective endocarditis may be connected with location of infection source and genetic factors.
Резюме. Изучали содержание связанных с ОБМ антител (иммунокомплексов ОБМ) в сыворот-ке крови при гестозе различной степени тяжести по сравнению с физиологической беременностью и небеременными женщинами. Концентрацию IgG-антител, связанных с ОБМ, определяли имму-ноферментным методом. Установлено, что у небеременных женщин и при физиологической бере-менности в сыворотке крови находится около 0,05 мкг/мл антител класса IgG, связанных с основ-ным белком миелина. Развитие легкого гестоза сопровождается повышением их сывороточной концентрации в 2-3 раза. Усугубление тяжести гестоза приводит к ее дальнейшему прогрессирую-щему подъему, так что максимальная концентрация комплексов (0,8 мкг/мл) определяется при пре-эклампсии и эклампсии. В постэкламптический период их количество снижается вдвое. Показатель концентрации антител класса IgG, связанных с основным белком миелина, в сыворотке крови при гестозе может использоваться для оценки степени тяжести гестоза и прогноза риска возникновения эклампсии.Ключевые слова: основной белок миелина, иммунокомплексы, беременность.
Levchenko V.G., Maltseva N.V., Lykova O.F., Konysheva T.V., Zorina V.N.
Contents of serum myelin basiC protein-igG antibodies Complexes in normal preGnanCy and Gestosisabstract. Serum levels of myelin basic protein (MBP)-bound immune complexes were studied in blood sera from women with gestosis, as compared with those in normal pregnancy and non-pregnant woman. The amounts of IgG-MBP complex in blood serum were determined by enzyme immunoassay using isolated anti-МBP-antibodies. The study has shown that about 0.05 mcg of IgG ml of blood serum are associated with myelin basic protein in unpregnant women or in normal pregnancy. Mild gestosis is accompanied by a 2-3-fold increase in MBP immunocomplex concentrations in blood serum. More severe stages of gestosis are characterized by its further rise, thus achieving maximal values of such MBP immune complexes (0.8 mcg/ml) in patients with pre-eclampsia and eclampsia. Their amounts were reduced twice after the periods of eclampsia. Serum levels of MBP-bound IgGs may be used to determine severity of gestosis and to predict a risk of eclampsia in pregnant women. (Med. Immunol., vol. 12, N 1-2, pp 155-160)
The effect of blood substitute perftoran on the content of alpha(1)- and alpha(2)-macroglobulins in the plasma and exudate was studied in rats with acute exudative inflammation. After intravenous injection of perftoran macroglobulin content increased in the plasma, but remained unchanged in the peritoneal fluid.
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