Научная статья на тему 'Сharacteristics of the cellular immunity in HIV-infected patients with pyoderma'

Сharacteristics of the cellular immunity in HIV-infected patients with pyoderma Текст научной статьи по специальности «Фундаментальная медицина»

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Текст научной работы на тему «Сharacteristics of the cellular immunity in HIV-infected patients with pyoderma»

Section 8. Medical science

8. Babadjanova G. S. Pathogenetic aspect of reproductive function disorders, its correction and prognosis of healthy children in women with some kinds of chronic TORCH infections.//Doctoral disser. Т. 2002. 285 p.

9. Blaghush P. Factor analysis with summary. - М.: Finances and statistics, 1989. - 248 p.

10. Borovikov V P., Borovikov I. P. Statistica: Statistic analysis and processing of the data in Windows. - М.: IID “ «Филинъ», 1997. - 608 p.

Azizov Bakhadyr, Tashkent State Institute of Dentistry E-mail: Dr.azizov@rambler.ru

Characteristics of the cellular immunity in HIV-infected patients with pyoderma

Immune system, being one of the major homeostatic systems, occupies the central place in the development of adaptation response to effects of the factors of an environment, with which the human body meets in the various periods of ontogenesis.

Pyoderma is one of the most widespread nosologies, accounting for to 40% of all cases of skin diseases [1]. Despite of distinctions in etiology, clinical picture, morphological changes and outcome, all pustular diseases, nevertheless, are unified by one common pathogenic mechanism — deviations in the immune system that has been confirmed by the numerous evidences [4; 5]. It is real, as the skin is considered as to be a component of immune system. As an immune organ it is capable of isolation, pressing, antigen presentation, production of immunoregulatory cytokines and development both of the local immune response and of the common, systemic to the antigens penetrating to the human organism. [9]. The high migration ability of the immune competent cells provides persistent connection of the skin to the central organs of im-munogenesis. Any disorder of the skin integument integrity results in activation of immunocompetent skin cells providing elimination of local aggression and formation of immune memory [6; 8].

The lesions of skin and mucous environments at a HIV-infection are considered as the constant manifestations of the clinical picture, they occur in 84% of the patients [7]. From twelve AIDS-indicator diseases five apply to the skin pathology. In dynamics of HIV-infection the lesions of skin and mucous membranes have recurring character, with the periods of aggravations and remissions, and gain heavy, not peculiar to their clinic variants in the advanced forms of disease [10; 11].

In the patients with pyoderma with HIV-infection there are revealed various variants of immune deviations — from immune deficit to activation of some parameters in Т- or B-cellular populations, which are interpreted differently. Some researchers state the point of view, according to which immune disorders are found only in the patients with heavy clinical course of dermatosis. At staphyloderma some authors note inhibition of Т-cellular immunity, others — its activation [2; 3]. The similar data are received during study of humoral immunity at the various forms of pyoderma [12; 14].

The purpose of research was to study parameters of cellular immunity in HIV-positive patients with primary and secondary pyoderma.

Materials and methods. Under supervision there were 71 HIV-infected patients at the age offrom 18 till 35 years, median was 27,7±1,3 years. The first group included 34 patients with the primary deep pyoderma, group two was constituted by 37 patients with secondary pyoderma. Group of the control consisted of 21 healthy volunteers, comparable by age and sex. The immunological investigations were performed on 1-2 day of admission to the hospital.

The immunological investigations were performed in the laboratory of immune cytokines of the Institute of Immunology of the Academy of Sciences of the Republic of Uzbekistan according to the methodical recommendations developed in the Institute of Immunology of the Ministry of Health of the Russian Federation and in the Institute of Immunology of the AS RUz (1992, 2001). Phenotype of immunocompetent cells was determined with use of monoclonal antibodies of the Joint Venture Ltd. “Sorbent” of the Institute of Immunology MH RF with method of indirect rosette using stabilized erythrocytes.

Results and discussion.

During study of HIV-infected patients with primary and secondary pyoderma at admission to the hospital there was observed tendency to the reliable reduction of the cellular immunity in comparison with healthy participants (Р < 0,001). The results of study were presented in Table 1. The reliable differences between patients from group 1 and 2 were not found (Р> 0,05).

In both groups of the patients the contents of relative and absolute parameters of lymphocytes was registered, on the average, reliably lower the control values (Р < 0,001). We did not reveal reliable differences in the contents of lymphocytes in pyoderma, divided into groups depending on the clinical form of disease (Р> 0,05).

Evaluation of the parameters of T-cellular immunity in the patients with HIV-infection, associated with secondary pyoderma, allowed to establish the tendency to decrease (Р < 0,001) ofrelative Т-lymphocyte counts with phenotype CD3 + (47,6±1,12%) in comparison with control group (59,3±1,1%).

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Characteristics of the cellular immunity in HIV-infected patients with pyoderma

In the patients with primary deep pyoderma there was noted sharp decrease in the relative contents (Р < 0,001) in blood of CD3 + lymphocytes (42,3±1,05%) and it was reliably lower than results of the studied patients of group 2 (Р < 0,001), 1482 ± 24 cells/pl and 1293 p 47 cells/pl, respectively.

It should be noted that during study of immune status the assessment of absolute parameters seemed to be more informative, because it characterizes the real CD3 + lymphocyte counts, circulating in blood of the studied patients. The received results of CD3+lymphocyte counts in the patients with HIV-infection, associated with primary pyoderma indicated about significant reduction of their absolute counts (Р < 0,001), that consequently was 3,3 times less than control parameters of the healthy persons. It is interesting, that in the patients with secondary pyoderma the decrease of the absolute counts of CD3 + lymphocytes (482 ± 24) was noted 2,7 times more rare. The difference was reliable in comparison with the first group and with healthy persons (Р < 0,05; Р < 0,001), respectively. The decrease in the counts of CD3 + lymphocytes occurs, mainly, at the expense of decrease in CD4 + lymphocytes.

HIV has increased tropism to Т-lymphocytes and other cells containing co-receptors, having structural similarity with CD4 + (Т-helpers, B-cells, monocytes, macrophages). This is explained by extremely high affinity of gp120 virion to coreceptor CD4, distributed on the surface of CD4 + lymphocytes [15].

The counts of relative and absolute parameters (CD3+ and CD4+) of helpers in the healthy people was in limits from 24 to 44% and from 532 to 1127 cells/pl with mean value 32,3 ± 1,1% and 704±32 cells/pl.

Is was established more expressed (Р < 0,001) reduction of relative counts of immunocompetent cells with phenotype (CD3+CD4+) in the patients with HIV-infection, associated with primary pyoderma, in comparison with the patients with secondary pyoderma (Р<0,05). As against relative parameters in HIV-infected patients, the absolute parameters of CD4+lymphocytes were reduced more marked. The difference was reliable between the patients of the first group and healthy participants (Р < 0,05; Р < 0,001), respectively.

Immunophenotyping of mononuclear (CD3+CD8 +) cells including Т-ccytotoxic lymphocytes in the patients with associated pathology of deep pyoderma with HIV infection allowed to establish, that their relative counts (22,2±0,76%) increased significantly (Р < 0,001) and was higher 1,4 times than the normative references (16,4±0,7%). The similar data of increases of the relative counts of CD3+CD8 + lymphocytes were noted in the patients in the second group (20,4±0,75%), but these changes had less expressed character and exceeded

1,2 times the parameters of norm (Р> 0,05).

One of the informative parameters during study of immunological status is study of IRI, the ratio CD4/CD8. At such approach there is found more latent disorder in the immuno-regulatory subpopulations of T-lymphocytes (9). The examinations showed that IRI of the healthy people accounted for

from 1,22 to 3% with mean value 2,01±0,09%. As it is visible from the table submitted, during study patients from group 1 and 2 at their admission to the hospital there was revealed reliable decrease in IRI in comparison with control group (Р < 0,001). The parameters of change between groups had no statistically reliable character (Р>0,05). Hence, in the patients with pyoderma and HIV-infection the deeper immuno-dysproportions were recorded with decrease of the contents of Т-helpers in the blood and increase of relative parameters of cytotoxic Т- lymphocytes.

As it is known, if the quantitative and functional parameters of Т-suppressors are higher than of Т-helpers, then the real conditions for development of immune deficit state have been created. The shift of this ratio to the left — is lower than 1,5 (in our case IRI is lower — 1,0) — such immunoregu-latory index is characteristic for immunodeficit conditions, especially for AIDS [13].

In turn NK-lymphocytes which are involved both in specific, and in unspecific parts of immunity in our researches showed the following results. The comparative analysis of the counts of NK- lymphocytes with phenotype (CD3-CD16+) in the patients with associated pathology in the first group showed that the relative counts of the natural killers was increased 1,4 times (16,2±1,1%), in comparison with the control (11,5+0,67). It is necessary to note that at secondary pyoderma with HIV infection in the studied patients there was observed more marked (1,7 times) increase in quantity of (CD3-CD16+) lymphocytes (Р < 0,001) in comparison with the appropriate normative references. The parameters of changes between groups also had statistically reliable character (Р < 0,001). It is connected, most likely, with the fact that such parameters are characteristic for polymicrobic etiology at the secondary pyoderma with the HIV infection in comparison with associated pathology of the deep pyoderma with HIV infection where the monoinfection took place mainly. However, in the patients of both groups the absolute parameters were reduced in comparison with the control data by 1,7 and 1,2 times (Р < 0,001), respectively.

In the patients of the first and second groups the relative values of marker CD25 + were reduced. The lowest level of CD25 + markers was observed in the patients of group 1-16,2±1,1% and 149±14,2 cells/pl, that was reliably lower (1,7 times) in comparison with parameters of control group (Р < 0,001). The absolute values decreased even more and were registered 4,1 and 3,2 times lower than the control data (Р < 0,001), respectively. These data indicated about inhibition of the functional activity Т-lymphocytes helpers. The decrease in the serum concentration of beta-2 microglobulin and its CD25 (receptor IL-2) correlated with intensity of HIV replication and velocity of the disease progressing in the patients with pyoderma with HIV infection.

The measurement of the quantity of all lymphocytes, expressing activation marker CD38 + allowed to establish moderate growth of lymphocytes with receptors CD38+, exceeding parameters of the control, their contents in the patients

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Section 8. Medical science

of group 1 were 1,7 times higher (Р < 0,001). The change of CD38 + positive lymphocytes in the second group was observed in a lesser degree in comparison with group 1 (Р < 0,05) and parameters higher in comparison with the control group (Р < 0,001). The literature data about estimation of the expression of the activation marker CD38 on the lymphocytes CD8 correlates with a level viremia (10), and in some reports — with the velocity of disease progressing [14; 15]. This is also concerns expressions of CD38 on the lymphocytes CD4 [6]. Besides, expression of CD38 was inversely proportional to increase of CD4 lymphocyte counts as response to antiretroviral therapy [7]. The data of the populational investigations support the model, according to which HIV replication stimulates immune system, that contributes to destruction of lymphocytes CD4 [11].

The counts of relative and absolute parameters of CD95 + lymphocytes in the healthy people were in limits from 19 to 35% and from 372 up to 867 cells/pl with mean values 25,7±0,94% and 559±25 cells/pl.

The data received from the analysis of the counts of lymphocytes expressing CD95 +, inducing apoptosis of cells in the patients of the first group showed that the relative counts of natural CD95 + cells increased by 1,3 times in comparison with the control. It is necessary to note that in the studied patients in the second group there was observed more marked (1,4 times) increase in (CD95 +) lymphocytes (Р < 0,001). However, the relative parameters between groups had no statistically reliable character (Р>0,05), while the absolute quantity of these cells had only tendency to decrease in comparison with control group (Р < 0,001). Thus, it is obvious,

that qualitative and quantitative disorders of the expression of lymphocytes CD25+D38 + and CD95 + receptors were key and critical in progressing of AIDS in pyoderma with HIV infection.

The determination of the counts of B-lymphocytes (CD20 +) in the patients with HIV associated with deep pyoderma allowed to establish reliable (Р < 0,001) increase of their relative counts (26,7±0,93%). In the patients of the second group there was observed increase in the greater degree in comparison with group 1 (P < 0,05) and control (P < 0,001). And their absolute counts in the patients with HIV decreased in both groups (P < 0,001) in comparison with norm (21,7±0,56%; 472±21 pl/ml). In the patients of the first group the more deep deficit of the counts of CD20 + lymphocytes was observed — 1,3 times more in comparison with group 2 and 2 times more in comparison with norm (Р < 0,001). It is connected, probably, to unspecific activation of the relative counts of CD20 + lymphocytes in the patients because of the raised level of endogenous protein and polysaccharide stimulators of B-lymphocytes, characteristic for bacterial pyoderma in HIV infection.

Conclusion. It is necessary to note, that during performance of the comparative study of some immunological parameters there were established the most informative prognostic criteria of the fast progressing HIV-infection in the patients with pyoderma. They were presented by significant reduction of the counts of Т lymphocytes, including helper cell subpopulation (CD3+CD4 +), increase in counts of Т-cytotoxic lymphocytes, expressing CD38 (CD8+CD38 +) and lymphocytes with receptors of Fas-apoptosis CD95 +.

Table 1. - Immunity parameters and markers of lymphocyte activation in the blood of the HIV-infected patients. (at admission)

Parameters Control group, n=21 Group 1, n=34 (Primary deep pyoderma) Group 2, n=37 (Secondary pyoderma)

Leucocytes abs 6459± 161 3790± 115** 3986±115**

Lymphocytes in% 33,7 ± 0,66 24,3±0,64** 25,4±0,60**

abs 2177±65 921±38** 1013±34**

CD3 in% 59,3 ± 1,1 42,3±1,05** 47,6±1,12**~

abs 1293 ± 47 1391±22** 1482 ±24**^

CD4 in% 32,3± 1,1 18,1±0,74** 21,2±0,83**^

abs 704± 32 174±14** 215 ±14**^

CD8 in% 16,4 ± 0,7 22,2±0,76** 20,4±0,75**

abs 358 ± 21 204±11** 207 ± 8,1**

CD4/CD8 in% 2,01 ± 0,09 0,98±0,04** 1,07±0,06**

CD16 in% 11,5 ± 0,67 16,2±0,58** 19,9±0,68**~

abs 251 ± 19 148±7,2** 201±8,4**~

CD 25 in% 27,9 ± 1,23 16,2±1,1** 18,7±0,91**

abs 608 ± 28 149±14,2** 189±15**

CD 38 in% 23,1 ± 0,78 39,2±1,42** 34,9±1,08 **•

abs 500 ± 19 361±11** 353±11**

CD 95 in% 25,7 ± 0,94 34,2±1,23** 36,5±1,14**

abs 559 ± 25 315±11** 369±12**"

CD 20 in% 21,7 ± 0,56 26,2±0,93** 30,6±0,99**^

abs 472 ± 21 241±10,4** 305 ±12,07**-

Note: Reliability of difference from control. * - P< 0,05; ** - P< 0,001; and from data of group 1 (••- P<0,001; • - P<0,05).

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The structure of neural psychological disorders in patients with symptomatic and idiopathic epilepsy

References:

1. Yakubov Sh., Davudyan M., Zalyalieva M. et al., 2000. “ HIV infection in Uzbekistan, “ Journal of Theroretical and Clinical Medicine [Journal Teoreticheskoy I klinicheskoy Medicini], in Russian, No2. P. 13-17.

2. Zalyalieva M. V. Immunitet pri VICH infeccii. 2002Journal of Theroretical and Clinical Medicine. [ Jurnal Teoreticheskoy I klinicheskoy Medicini], in Russian, No3. P. 41-43.

3. Budavari J. M., Graysin W. Popular follicular eruptions in human immunodeficiency virus-positive patients in South Africa. 2007. [Int.J. Dermatol. Jul], No4697. P. 706-710.

4. Vitous A., Hosbatova J. Infectious diseases in problem drug users hospitalized in the infectious ward of the Motol University Hospital in 2002-2005. 2007. [Klin. Microbiol Infect Lek.], No Apr; 13 (2). P. 70-75.

5. Tan H. H., Tan A., Theng c., Ng S. K. Cutaneous Mycobacterium haemophilium infections in immunocompromized patients in a dermatology clinic in Singapore. 2004. [Ann. Acad. Med. Singapore.] No Jul; 3394. P. 532-536.

6. Cucalo S.V et al. The new approaches to the treatment of pyoderma. Vestnik of poslediplomnogo medicinskogo obrazovania. 2009; N 2. [Novie podhodi k lecheniyu piodermii].

7. Potekaev N. S. Skin lesions in HIV infection. Vestnik dermatologii I venerologii. 1991; № 7: 59-66. [Porageniya koji pri in-fekcii VICH]

8. Isaev M. S. et al. Bactericidal activity, microbic number, microbic landscape in the patients with pyoderma living in the various climatic and geographic zones of Tajikistan. Book ofAbstracts: The 5th Congress of Dermatovenerologists of Uzbekistan, Tashkent, 20-08. The collection of jobs, 5 congresses дерматовенерологов of Uzbekistan, Tashkent 2008.

9. Pettov R. V, Khaitov R. M. Immunology and infection. Manual book for physicians. Moscow. 1998.

10. Pokrovskiy V. V. Epidemiological aspects of HIV/AIDS. Moscow Med.Jurn. 2000; 1: 19-21. [Epidemiologicheskie aspe-kta VICH/CPID].

11. Sabirov U.Yu. Prevalence, structure of cutaneous-mucous lesions and diseases sexually transmitted, pathogenesis of urogenital chlamidiosis in HIV-infected patients. Synopsis of the dissert. for scientific degree “Doctor of medical sciences" Tashkent, 2008.

12. Intermediate term estimation of the Strategic Program on counteraction to distribution of HIV-infection in the Republic of Uzbekistan for 2007-2008 years. Tashkent, 2010.

13. Nobl U. K. Microbiology of human skin. Moscow,1986.

14. Shinaev N. N. Disease of skin and mucous membranes as AIDS expression in the Africans. Moscow, 2008.

15. Sud N, Shanker V, Sharma A, Sharma NL, Gupta M. Mucocutaneous manifestations in 150 HIV-infected Indian patients and their relationship with CD4 lymphocyte counts. 2009 Nov; 20 (11): 771-4.

Azizova Rano Bakhodirovna, Assistant of the Department of Nervous Diseases of the Tashkent Medical Academy E-mail: mbshakur@mail.ru

The structure of neural psychological disorders in patients with symptomatic and idiopathic epilepsy

Abstract: Symptomatic and idiopathic forms of epilepsy have several differences in neural psychological values. The most expressed cognitive deficit in the form of cognitive disorders is characteristic for patients with symptomatic epilepsy. The absence of inter-hemisphere asymmetry of P300 wave amplitude was revealed in cases of idiopathic and symptomatic forms, indicating functional disorders.

Keywords: epilepsy, cognitive disorders, cognitive-induced potentials

The problem of epilepsy is still in the center of scientist-neurologist attention. It is linked with not only variety of neural physiologic peculiarities of the disease, diversity of clinical progress, but also with various complications developing together with regular administration of antiepileptic agents [2; 3].

Recently the number of publications, dedicated to the study of cognitive functions in cases of various neurologic

diseases, is increasing. The problem of cognitive deficit increase was considered in close link with progressing of the pathologic process, including epilepsy in adults. In 30-50% of patients with epilepsy psycho-neurological disorders [1] were observed. Among these disorders there were cognitive, affective and behavior ones and disorders of the highest psychic functions, including those linked with inadequate and inopportune administration of antiepileptic agents (AEA) [6; 9].

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