Abstract.  The  review  article  concerns  various  features  of  PAX-5  (paired  box  5)  transcription  factor,  its structure, functions, regulation of activity, involvement into differentiation and activation of B lymphocytes, switching to IgE synthesis, its role in oncogenesis, and a putative role of this factor for development of bronchial asthma.

Further  insight  into  specific  properties  of  PAX-5  factor  in  bronchial  asthma  may  provide  a  promising approach to studying mechanisms of this disorder. (Med. Immunol., 2011, vol. 13, N 6, pp 569-580)

Abstract.  Chemokines  are  a  key  factor  that ensures  the  participation  of  different  cell  types  in the  immunological  protection  of  mucosa.  In  our study  we  chose  some  chemokines  that  ensured  the chemotaxis of neutrophils (CXCL8/IL-8), eosinophils (CCL11/eotaxin,  CCL24/eotaxin-2),  monocytes  and T-lymphocytes  (CCL3/MIP-1α,  CCL4/MIP-1β, CCL5/RANTES),  as  well  as  their  receptors  (CCR1, CCR3, CCR5, CXCR1, CXCR2). mRNA expression of  chemokines  and  their  receptors  in  nasopharyngeal mucosa brush-biopsy specimens determined by RT-PCR in healthy persons, the level of the same chemokines in serum determined by multiplex chemiluminescent assay were analyzed according to smoking. The level of mRNA expression of IL-8 (p < 0.001) and RANTES (p < 0.001) in nasopharynx brush-biopsy specimens and  serum  levels  of  IL-8  (p  <  0.0001)  of  smokers  were  significantly  lower  as  compared  with  nonsmokers. Correlation analysis showed the dependence of the chemokine synthesis on the factor of smoking: the index of smoking (pack/years) is negatively correlated with mRNA levels of IL-8 (r = -0,67 p = 0,003) and RANTES (r = -0,58, p = 0,015) in nasopharynx brush-biopsy specimens and serum concentration of IL-8 (r = -0,89, p = 0,0000002). Thus, these data offer that smokers manifested a defect of the local synthesis of RANTES and IL-8 in nasopharyngeal mucosa in combination with systemic defect of IL-8 production in peripheral blood, that can lead to chronization of bacterial infection and prolonged persistence of viral infection. (Med. Immunol., 2011, vol. 13, N 6, pp 617-622)

 

Abstract.  Autoimmune  thyroiditis  (Hashimoto’s  thyroiditis,  HT)  still  represents  an  unresolved  problem of modern endocrinology, since its etiology and pathogenesis are yet unclear. Cytokines play an important role in the regulation of immune and inflammatory response, therefore, some gene variants encoding them, are considered as potential risk risk factors for autoimmune thyroid diseases. We have genotyped 298 women from the Republic of Tatarstan (RT, control group, 137 persons; HT patients, 161) for the following gene polymorphisms: interleukin-1 beta (IL-1β) +3953 C/T (rs 1143634); interleukin 4 (IL-4) -590C/T (rs 2243250), and interleukin 6 (IL-6) -174C/G (rs 1800795), using allele-specific PCR. The results showed a significantly increased frequencies of C allele (P  = 0.0003) and CT genotype (P  = 0.048, OR  = 6.05, 95%CI 2.59-2.97) of  +3953  C/T  of  IL-1β  in  patients  with  Hashimoto's thyroiditis, as compared with control group. The latter  group showed higher prevalence of T allele (P  = 0.0003) and TT genotype (P  = 4.95 Ч 6.10; OR  = 0.15, 95%CI 0.06-0.38). The 590C/T and -174C/G polymorphic variants in, resp., IL-4 and IL-6 genes are not associated with increased risk of this disease among women from RT. (Med. Immunol., 2011, vol. 13, N 6, pp 603-608)

 

Abstract. TRAF3IP2 gene plays an important role in the processes of inflammation and autoimmune control. TRAF3IP2 protein acts as a signal transducer from membrane receptors to the cell nucleus and is essential for the biological effects of Th17-lymphocytes. The goal of present study was to investigate distribution of allelic variants of TRAF3IP2 Arg74Trp polymorphism as a risk factor in psoriasis development, and to evaluate TRAF3IP2  mRNA  expression  levels  in  psoriasis  patients  and  healthy  donors.  Peripheral  blood  leukocytes were used as a source of DNA. Gene testing was performed for 261 patients and 482 healthy blood donors by real-time allele-specific PCR. TRAF3IP2 mRNA expression was measured in the skin biopsy samples from 36 patients with psoriasis and 14 healthy donors by means of quantitative reverse transcriptase PCR, using a paired-sample approach with SDHA reference gene. We have observed a significantly increased occurrence of rare Trp allele, with 10.5% among psoriasis patients (55/522), as compared with 7.0% (67/964) for healthy persons (OR = 1.58, 95% CI: 1.09 – 2.28, р = 0.02). A trend of higher Trp allele occurrence was revealed in patients with severe psoriasis – 21/154 (13.6%) when compared to the patients with milder course of the disease – 34/368 (9.2%) (р = 0.14). No differences were found for TRAF3IP2 mRNA expression in skin samples from psoriasis patients versus healthy persons. The association between TRAF3IP2 Trp allele and increased susceptibility to psoriasis suggests that Trp variant of this protein may display a higher enzymatic activity. Induction of inflammatory process in carriers of Trp allele would be more intensive, thus being a predisposing factor in psoriasis development. (Med. Immunol., 2011, vol. 13, N 6, pp 597-602)

 

Abstract. Adhesion to blood vessel endothelium is an important stage of leukocyte migration. This study was aimed for studying the effects of supernates from ultrasound-destroyed Streptococcus pyogenes (SUDS) upon adhesive properties and adherence degree of THP-1 myelomonocytic leukemia cells to EA.hy926 endothelial cells. After 24-hour incubation of THP-1 cells with SUDS, a reduction in CD49d expression levels on these cells is observed. Plastic adherence of endothelial cells was reduced in presence of SUDS, whereas similarly treated THP-1 cells become more adherent to plastic surfaces. A 24-hour pre-incubation of THP-1 cells with SUDS resulted in reduction of their adherence to endothelium, either with SUDS-treated, or non-treated endothelium cultures. Prolonged incubation of endothelial cells with SUDS caused an increase in adherence of intact THP-1 cells to endothelium. Hence, the adhesion properties of endothelial and THP-1 cells are changed in different ways under the influence of streptococcal components. Such variability may be due to involvement of different cellular receptors for monocytes and endothelial cells during recognition of bacterial components. (Med. Immunol., 2011, vol. 13, n 6, pp 581-588)

 

Abstract.  Associations  between  I105V  and  A114V gene  polymorphisms  of  glutathione-S-transferase P1  and  levels  of  IgE  and  secretory  IgA  in  tear  fluid were  studied  in  steelworkers  with  or  without  ocular diseases,  as  compared  with  healthy  office  employees. Genotyping was performed by means of allele-specific polymerase chain reaction, whereas ELISA technique was used for immune testing. We have found that IgE levels in tear fluid was increased in steelworkers with dystrophic eye diseases, pinguecula/pterygium, and healthy steelworkers, in comparison with control group. This increase correlates with pinguecula/pterygium size and with their industrial employment terms. Secretory IgА levels in tears were decreased in these groups of workers, as compared with controls. Concentrations of both  immunoglobulins  in  tear  samples  depended  on  I105V  and  А114V  glutathione-S-transferase  P1  gene polymorphisms. I105V polymorphism correlated with lower concentrations of tear IgЕ in steelworkers with ocular  dystrophic  diseases  and  healthy  metallurgists.  А114V  polymorphism  is  connected  with  decreased quantities of tear IgЕ in steelworkers with ocular dystrophic diseases, as well as with the lower amounts of secretory  IgА  in  healthy  workers  and  administrative  staff.  Hence,  polymorphic  loci  I105V  and  А114V  of glutathione-S-transferase P1 gene may exert a modulatory effect upon biosynthesis of both Ig types. (Med. Immunol., 2011, vol. 13, N 6, pp 609-616)

 

Abstract.  Leukocyte  recruitment  to  placental  tissue  is  an  important  factor  of  its  development.  In  this respect, adhesion molecules at the endothelial cell surface represent a key determining factor of leukocyte adhesion and their trans-endothelial migration. The goal of investigation was to evaluate changed expression of adhesion molecules on the endothelial cells induced by supernates of placental tissue cultures. Placental tissue supernatants produced by the first- and third-trimester placental tissue from normal pregnancy, as well as from women with gestosis, induced higher expression of CD31, CD9, CD62E, CD62P, CD34, CD54, CD51/61, CD49d  and  integrin  β7  expression  by  endothelial  cells,  as  compared  with  their  baseline  levels.  However, the  supernates  from  pre-eclamptic  placental  tissue (3rd  trimester)  caused  an  increased  CD9  expression by  endothelial  cells,  as  compared  with  effects  of placental  supernates  from  eclampsia-free  cases.  Our data  contribute  to  understanding  a  possible  role  of endothelial cell adhesion molecules in recruitment of leukocytes to placental tissue and possible participation of adhesion molecules in pathogenesis of pre-eclampsia. The work was supported by a grant from Russian Ministry of Education and Science ГК №02.740.11.0711 and Presidential grant № НШ-3594.2010.7 and МД-150.2011.7. (Med. Immunol., 2011, vol. 13, N 6, pp 589-596)

Abstract. Application of flow cytometry (FC) techniques has considerably expanded the opportunities for evaluation of immune cells, aiming for better diagnostics of immunodeficiency disorders, autoimmune and lymphoproliferative diseases, etc.

A procedure of laboratory testing is subdivided into several stages, i.e., pre-analytical, analytical and post-analytical. At present, some strict criteria are developed for inclusion of various cell parameters into a diagnostic set, along with operational algorithms, in order to optimize the FC procedures. However, the percentage of errors in FC assays still remains high. More than a half of the errors originate from pre-analytical stage.

The recommendations listed in this article should definitely influence quality of laboratory investigations and improve diagnostics of immune functional disorders, thus providing adequacy of therapeutic prescriptions. (Med. Immunol., 2011, vol. 13, N 6, pp 639-646)

 

Abstract. We studied immune markers of diabetes mellitus, as well as their relations to clinical features at the onset of disease. The patients with newly diagnosed diabetes were examined. Antibodies to glutamate decarboxylase, islet-cell cytoplasm antigen, along with antibodies to insulin and basal C-peptide were tested. Immunological markers of type 1 diabetes mellitus have been identified in 58% of cases. The immune markers of type 2 diabetes mellitus have been discovered in 47.5% of cases. (Med. Immunol., 2011, vol. 13, N 6, pp 623-626)

Abstract. Functional activity of neutrophylic granulocytes from whole blood of the children with acute  lymphoblastic leukemia was tested by means of luminolnduced chemiluminescence detection. We haverevealedincreased production of reactive oxygen species under basal conditions, and a decreased chemiluminescent  response after zymosan-induced stimulation. (Med. Immunol., 2011, vol. 13, N 6, pp 631-634)

 

Abstract. Blood serum levels of cytokines (Il-1β, TNFα, IL-2, IL-4, IL-6, IL-8, IL-10, IL-20, IL-23),  cytokine soluble receptors (SRp55 TNFα, SR IL-6), as well as markers of insulin resistance were studied in  a group of male patients with primary gout. Increased levels of the above cytokines and deficiency of soluble  IL-6 receptors in blood serum were most pronounced in gouty patients with insulin resistance syndrome. Close  links were revealed between serum uric acid and insulin contents in gouty patients. Significant correlations were  found between the levels of insulin, some cytokines (IL-4, IL-6, TNFα), and soluble receptors (SRp55 TNFα,  SR IL-6), thus presuming a certain role of impaired cytokine profile for development of insulin resistance  syndrome in such cohort of patients. (Med. Immunol., 2011, vol. 13, N 6, pp 627-630) 

Abstract. We investigated effects of combined oral contraceptives (COC) containing low- and microdoses of estrogenic components upon serum levels of macroglobulin family proteins (alpha-2-macroglobulin, α2-MG, and pregnancy-associated alpha-2-glycoprotein, α2-PAG), their immune complexes with IgG, as well as concentrations of some cytokines (IL-1β, IL-6, TNFα, IFNγ). It was shown that cytokine levels did not differ with control, whereas α2-MG concentrations showed a time-dependent decrease in a group of women taking COC with microdoses of estrogens, and α2-PAG levels increased tenfold, independent on dosage and time of COC application. Meanwhile, contents of PAG-IgG complexes exhibits a gradual decrease, along with increase in MG-IgG. Considering PAG as a marker of normal and malignant proliferation, we suggest, that the levels of α2-PAG may be useful in monitoring of women taking COC, in order to predict high risk of pathological  proliferation  by  evaluation  of  individuals with  elevated  α2-PAG  levels.  (Med.  Immunol.,  2011, vol. 13, N 6, pp 635-638)

 

Abstract.  The  lecture  presents  current  data,  as  well  as  authors’  view  to  the  issue  of  immune  system involvement into inflammation. General physiological principles of immune system functioning are considered in details. Immunological mechanisms of local inflammation and participation of immune system components are analyzed with regard of protective/adaptive reactions in inflammatory foci. Original formulations of basic concepts are presented from the viewpoint of pathophysiology, immunopathology and clinical immunology, as being applied to the issues discussed. (Med. Immunol., 2011, vol. 13, N 6, pp 557-568)