Volume 03 Issue 08-2023
25
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
ABSTRACT
The goal was to study the state of the immune system of children with laryngeal papillomatosis depending on the
clinical course of the disease in the dynamics of antiviral therapy. A comparative analysis of immunological parameters
was carried out in the dynamics of standard therapy (before and after), and after standard + immunotropic therapy.
For this purpose, 252 children with laryngeal papillomatosis aged 3 to 9 years were examined. All children were
examined and treated in the surgical department of otolaryngology of TMA. In order to determine the effectiveness
of the treatment of children, the following division into groups was carried out: Group I - children with a continuously
recurrent course of papillomatosis of the larynx were divided into two subgroups: Subgroup I - the comparison group
received standard treatment surgery + IFN preparations (reaferon) - one course per 28 days; Subgroup I - study group
surgery + IFN preparations (alpha-IFN / inosine) - according to the scheme for 1 year. Group II - children with a
frequently relapsing course of PH: II a subgroup - received standard treatment surgery + IFN preparations (reaferon)
- one course for 28 days; II in the subgroup - surgery + IFN preparations (alpha-IFN / inosine) - according to the scheme
for 6 months. Group III - children with a rarely recurrent course of PH: III a group - surgery; III in group - surgery +
likopid. Unidirectional changes in the state of the immune response in papillomatosis of the larynx were revealed,
which were most pronounced in the group of children with a continuously recurrent form of papillomatosis of the
larynx. In the dynamics of therapy, improvements in the indicators of cellular and humoral immunity were found;
KEYWORDS
Research Article
MODERN APPROACHES TO THE STUDY OF THE STATE OF THE IMMUNE
SYSTEM OF CHILDREN WITH PAPILLOMATOSIS OF THE LARYNX ON THE
BACKGROUND OF ANTIVIRAL THERAPY
Submission Date:
August 14, 2023,
Accepted Date:
August 19, 2023,
Published Date:
August 24, 2023
Crossref doi:
https://doi.org/10.37547/ijmscr/Volume03Issue08-05
Sh.A. Makhamadaminova
Tashkent Medical Academy, Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ijmscr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
Volume 03 Issue 08-2023
26
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
papillomatosis of the larynx in children, interferons, interferon inducers, cellular and humoral parameters of immunity.
INTRODUCTION
As is known from the literature, the diagnosis of
laryngeal papillomatosis, being a benign consequence
of a viral process, requires immunological studies,
ranging from cellular to molecular [2,4,16]. It has been
established that children with laryngeal papillomatosis
are characterized by dysfunction in the state of the
cellular and humoral parts of the immune system,
which are probably due to defects in one or more
immune response mechanisms. Thus, the presence of
a secondary immunodeficiency state is substantiated.
As is known, immunodeficiencies are independent
syndromes, characterized by a lack of immunity [1,6],
which is characterized by a tendency to acyclic course,
recurrence of the disease and the occurrence of
oncological pathology [ 10]. The very first and main
syndrome of the secondary immunodeficiency state is
the infectious syndrome, which is characterized by
chronic recurrent infection. Among all existing
syndromes of secondary immunodeficiency, the
infectious syndrome is the leading one, and in a
laboratory study, the infectious syndrome is
characterized by its own algorithm of immunological
changes, including defects in the state of cellular and
humoral immunity factors [1,6,10,11]. As it is already
clear, laryngeal papillomatosis refers to an infectious
syndrome of a secondary immunodeficiency state,
which is distinguished by all the signs of
immunodeficiency characteristic of it, and therefore
attracts great attention from researchers. In this case,
the theoretical justification was the previously
identified imbalance in the immune system and
deficiency in the system of functioning of the main
interferons of the immune system [9,12]. As for
treatment, it should be noted that, in general, the
evaluation of treatment results presents great
difficulties, which are primarily due to the diversity of
the clinical course of laryngeal papillomatosis in
children. According to the data obtained, it is known
that during the course of papillomatosis of the larynx
in children, spontaneous long-term remissions can be
observed, as well as rapid growth, which forms
frequently recurrent forms of the disease [1,2,5,7,14].
As for the immune status, there is a pronounced
imbalance in the populations of lymphocytes of the
immune system and immunodeficiency in the cellular
link of immunity [11,12,18].
In connection with the foregoing, we set a goal to
study the state of the immune system of children with
laryngeal papillomatosis, depending on the clinical
course of the disease in the dynamics of antiviral
therapy. In connection with the above, we carried out
a comparative analysis of immunological parameters in
Volume 03 Issue 08-2023
27
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
the dynamics of standard therapy (before and after),
and after standard + immunotropic therapy.
MATERIAL AND RESEARCH METHODS
We conducted immunological studies in 252 children
with larynx papillomatosis aged 3 to 9 years. All
children were examined and treated in the surgical
department of otolaryngology of the Tashkent Medical
Academy (TMA). In order to determine the
effectiveness of the treatment of children, the
following division into groups was carried out: Group I
- children with a continuously recurrent course of
papillomatosis of the larynx were divided into two
subgroups: Subgroup I - the comparison group
received standard treatment surgery
+ IFN
preparations (reaferon) - one course per 28 days;
Subgroup I - study group surgery + IFN preparations
(alpha-IFN / inosine) - according to the scheme for 1
year. Group II - children with a frequently relapsing
course of PH: II a subgroup - received standard
treatment surgery + IFN preparations (reaferon) - one
course for 28 days; II in the subgroup - surgery + IFN
preparations (alpha-IFN / inosine) - according to the
scheme for 6 months. Group III - children with a rarely
recurrent course of PH: III a group - surgery; III in group
- surgery + licopid . The control group was represented
by 29 practically healthy children of the same age and
gender.
Immunological studies of children were carried out on
the basis of clinical, laboratory and instrumental
methods of research before the appointment of
treatment, and during therapy after surgical removal at
6 months of therapy. Immunological studies were
carried out at the NDC "Immunogen-test" at the RNCI
of the Ministry of Health of the Republic of Uzbekistan
on the basis of a scientific agreement. Determination
of cellular, humoral immunity, as well as identification
of activation markers CD 38+, CD 95+ was carried out
using mAb in accordance with the methodological
recommendations developed by the Institute of
Immunology of the Russian Federation and the
Institute of Immunology of the Academy of Sciences of
the Republic of Uzbekistan [9]. The following research
methods were carried out: determination of the
number of leukocytes and lymphocytes, determination
of subpopulations of lymphocytes by determining CD
4+ - T-helpers, CD 8+ - T-cytotoxic lymphocytes, CD 16+
- natural killer cells, CD 20+ - B-lymphocytes, C D 38+ -
precursors of T- and B-lymphocytes, C D 95+ -
lymphocytes with a receptor for physiological
apoptosis,
determination
of
the
level
of
immunoglobulins of the main classes in blood serum
and determination of circulating immune complexes of
various sizes (CIC) by ELISA method.
The results obtained and their discussion. As
mentioned above, it is customary to consider
papillomatosis of the larynx in children as an
Volume 03 Issue 08-2023
28
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
immunodeficiency state, and in the literature it is
described as a disease related to secondary
immunodeficiencies in pathogenesis, due to the fact
that papillomatosis is a chronic recurrent virus-induced
process [7,8]. Therefore, the study of the state of
immunoreactivity
in
children
with
laryngeal
papillomatosis is an important factor necessary to
establish the depth and extent of the formation of
immunodeficiency, predict the disease, and most
importantly, identify the most radical ways of therapy,
including immunotropic therapy. In this regard, the
study of quantitative and functional factors of the
immune system, i.e. cellular and humoral parameters
of immunity in the dynamics of therapy is a global
problem in medicine [7,10,11,12,17]. Therefore, based on
the foregoing, we assessed the cellular and humoral
factors of the immune system in children with
laryngeal papillomatosis, depending on various forms
of the course of the disease in the dynamics of antiviral
and immunotropic therapy. Table 1 presents the results
of a comparative analysis of the immune status of
children with laryngeal papillomatosis in the course of
therapy. According to the data presented in the table,
in a comparative analysis of the cellular composition of
populations and subpopulations, certain changes are
observed between groups 1a and 1c. So, for children of
group 1c, where inosine was added in the complex,
when compared with the data of children of group 1a,
an increase in the expression of CD 3+ on lymphocytes
by 1.14 times, CD 4+ - by 1.15 times, a decrease in CD 8+
- by 1.14 times, IRI increased by 1.3 times, CD 16+ was
slightly reduced, but significantly. The study of humoral
factors of immunity revealed that immunoglobulin A in
peripheral blood serum was reduced by 1.7 times, CIC3%
was reduced by 1.7 times, CIC4% was reduced by 2.4
times. The differences identified were all significant.
Obviously, the decrease in the total pool of T-
lymphocytes ( CD 3+) was observed mainly due to the
suppression of the number of T-lymphocytes that
express CD 4+. It was found that the lowest content of
T-lymphocytes was found in the group of children with
continuously recurrent papillomatosis of the larynx
before treatment. At the same time, during therapy, an
increase in the total pool of T-lymphocytes is observed,
which positively affects the state of T-cell
immunodeficiency. Further, the content of the main
regulatory cell of immunity, T-helpers/inducers, was
studied. The CD 4+ T cell response to viral proteins is an
important mechanism of host defense, since CD 4+ T
helpers stimulate the production of antibodies by B
lymphocytes and activate CD 8+ T lymphocytes specific
for virus-infected cells [10]. The analysis revealed that,
during therapy, there was also a significant increase in
the expression of CD 4+ on T-lymphocytes compared
with the values of the control group and the group
before treatment (p<0.05). So it is known that
cytotoxic CD 8+ T-lymphocytes play an important role
in the pathogenesis of viral and proliferative diseases
[9,10]. Analysis of the expression of CD 8+ on T-
lymphocytes showed that during treatment there is a
Volume 03 Issue 08-2023
29
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
decrease in their expression, which confirms the
improvement in cellular immunity and a decrease in
suppression
against
the
background
of
immunostimulation. It should be noted that, according
to the literature, the virus is able to persist even in the
presence of CD 8+ lymphocytes, which becomes the
main mechanism of disease progression [8,10]. The
immunoregulatory index (IRI), which is the ratio of the
number of CD 4+T-helpers/inducers to the number of
CD 8+T-lymphocytes, is essential in secondary
infectious immunodeficiency states . Obviously, the
suppression of CD 4+T-helpers/inducers against the
background of an increase in the number of CD 8+T-
lymphocytes leads to a decrease in IRI. The smallest
reduced value of IRI is noted in the group of children
with a continuously recurrent form of laryngeal
papillomatosis compared with the values of the two
groups of children studied, and amounted to 0.8 ± 0.03
in the group of children with continuously recurrent
laryngeal papillomatosis, and in the control group - 1.49
± 0.02 (p<0.05). Obviously, a decrease in IRI is an
important criterion for the depth of T-cell
immunodeficiency
in
children
with
laryngeal
papillomatosis. Again, against the background of
therapy, the value of IRI increases significantly and is
reliably distinguishable.
Table 1.
The immune status of children with laryngeal papillomatosis in the dynamics of therapy depending on the clinical
features of the disease
(continuously relapsing group), М± m , %
Immunity
parameters
Norm
( n= 29)
Before
treatment
(n= 34 )
Group 1a
(standard + IFN
drug) ( n = 28)
Group 1c (standard
+ IFN + inosine
pranobex)
( n =26)
Leukocytes
6050±128.0
5910±114.5*
7200.5±165.8
8190.7±142.8
Lymphocytes
32.5±0.84
37.2±1.32*
41.5±0.92*^
42.8±1.12*#
CD 3+
58.4±1.25
42.4±0.98*
47.9±1.52* ^
54.6±1.42* #$
CD4+
38.3±1.25
30.5±1.33*
32.48±0.83* ^
37.5±1.34* #$
CD8+
18.8±0.54
33.80±1.18*
28.4±1.26* ^
24.80±0.88* #$
Volume 03 Issue 08-2023
30
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
IRI
1.65±0.05
0.72±0.02*
1.04±0.04 *^
1.32±0.02 *#$
CD 16+ _
18.2 1.0
3 _
28.4±0.14*
24.3±0.21*
22.02±0.42* #$
CD20+
19.9
0.83
2 6.6
1.26 *
2 3.5
1.2 2* ^
2 1, 4
1, 31* #
CD38 + _
22.4±0.86
27.8±1.24*
25.2±1.11*
22.8±1.30* #
CD95 + _
23.5±1.26
32.9
1.45*
27.3
1.42* ^
23.2
1.25* #
IgG
1260.0
21.60
1390.4±26.2*
1325.2±30.2*
1295.0±20.4* #
IgA
122.0
3.21
160.8
4.68*
152.4
2.85 ^
130.4
1.94 #$
IgM
112
2.1
138.4
1.61*
127.5
1.70 ^
119.2
1.46 #
CEC3%
8.58±1.34
198.2
3.72
145.4
2.28 ^
85.60
3.65 #$
CEC4%
14.22±1.51
158.5
2.45*
^
109.4
2.55* ^
45.80
3.15* #$
Note: * - significance of differences with the data of the control group, ^ - differences of group 1a with values before
treatment; # - differences in group 1b with values before treatment; $ - differences between 1a and 1c groups.
Next, we studied the number of natural killer cells
(NKCs), which are the third population of lymphocytes
that ensure the maintenance of genetic homeostasis,
which are phenotypically and functionally significantly
different from T- and B-lymphocytes [8,10]. We have
studied ECCs with CD 16+ phenotypes. Revealed a
significant increase in the relative number of CD 16+
ECC in laryngeal papillomatosis, with the largest
number of ECC found in the group of children with
continuously
recurrent
form
of
laryngeal
papillomatosis (p<0.05). Thus, in the group of children
with a continuously recurrent form of papillomatosis of
the larynx, the relative number of CD 16+ ECC was
28.4±1.3%, while in the control group it was 18.6-1.24 ±%.
According to the data in Table 1, against the
background of standard treatment, the number of ECC
decreased, and with the addition of an IFN inductor, a
significant decrease in ECC was observed and was close
to the normal values. The level of B-lymphocytes, the
main regulatory cells of the immune system, which is
important in the development of humoral immunity,
showed that the number of B-lymphocytes by the
expression of CD 20+ receptors involved in the
activation of B-lymphocytes was significantly increased
Volume 03 Issue 08-2023
31
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
in the group of children with a continuously recurrent
form of papillomatosis larynx in comparison with the
values of the control group (p<0.05). Moreover, it was
found that the highest content of B-lymphocytes was
also found in this group of children and amounted to
26.6 ± 1.2%, and in the control group - 19.4 ±0.72%, and
the lowest value of B-lymphocytes was found in the
group children with a rare recurrent form of
papillomatosis of the larynx. It is obvious that the
increased expression of CD 20+ on B-lymphocytes in
laryngeal
papillomatosis
indicates
the
active
participation of B-lymphocytes in the antiviral immune
response, but it should be noted that the protective
efficacy under conditions of virus persistence is limited
[3,6,10]. Despite this, the study of the content of B-
lymphocytes is an important criterion for assessing the
depth of immunodeficiency and determining the next
steps in terms of diagnosis and treatment of laryngeal
papillomatosis in children. During therapy, a gradual
decrease in the number of B-lymphocytes is observed,
especially in the group of children against the
background of adding an IFN inducer to the treatment
regimen. It is known that immunoglobulins play an
important function of mediators in the cascade
development of the immune response and can partially
determine the effectiveness of the final, effector
reactions of cellular immunity in inactivation and
elimination of viral antigens [1,10]. Also, it is known that
circulating antibodies are one of the effector factors of
immunity, providing antigen-specific protection
[4,10,12]. Serum concentrations of the main
immunoglobulins IgG, IgA, IgM were analyzed in
children with laryngeal papillomatosis depending on
the clinical course of the disease and in the dynamics of
therapy. Depletion of IgG was revealed in the group of
children with laryngeal papillomatosis with a
continuously recurrent form, the content of IgM was
significantly reduced in the group of children with a
continuously recurrent form compared with the data
of the control group and data of other groups. Analysis
of the IgA content revealed the presence of a
significant increase in IgA in the blood serum of all
children with laryngeal papillomatosis. Moreover, a
pronounced increase in IgA was noted in the group of
children with a frequently recurrent form of laryngeal
papillomatosis. Consequently, the death link of
immunity was characterized by an increase in serum
concentrations of Ig G and Ig A in the group of children
with laryngeal papillomatosis. Moreover, in the
dynamics of treatment, an improvement in
immunoglobulin parameters is observed, which once
again confirms the formation of an adequate humoral
immune response against the background of the use of
IFN preparations and IFN inducers.
From the available literature data, it can be seen that
the study of activation markers of lymphocytes is of
great scientific and practical importance, especially in
infectious diseases. analysis of activation markers of
lymphocytes makes it possible to study the processes
Volume 03 Issue 08-2023
32
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
of activation, proliferation, differentiation and
apoptosis
of
immunocompetent
cells
and
characterizes the cell cycles associated with these
processes [6,9,10]. Thus, we studied lymphocyte
markers, such as CD38+ and CD 95+. It is known that CD
38+ is an activation marker represented by a
transmembrane glycoprotein, which is considered as a
multifunctional protein [10]. CD38+ is the precursor of
plasma cells. It is expressed on immature T-
lymphocytes and B-lymphocytes, activated T-
lymphocytes, and plasma cells [6,10,12]. Analysis of the
study of CD38+ expression on lymphocytes revealed a
significant increase in this marker in groups of children
with larynx papillomatosis in comparison with the data
of the control group ( p<0.05 ). Moreover, the
difference in the expression of this marker was
significant in all groups of children. Thus, the
expression of CD38+ in the continuously relapsing form
of papillomatosis was 27.8±1.14%, and in the group with
the frequently relapsing form it was 29.2±1.40%, in the
group with the rarely relapsing form it was 31.4±1. 20%,
while the norm was equal to 23.4±0.58%. Thus, it can be
seen that the expression of CD38+ on lymphocytes
differed between the studied groups of children (
p<0.05 ). Therefore, the analysis showed that an
increase in the expression of CD38+ activation markers
in children with laryngeal papillomatosis indicates the
presence of activation of both cellular and humoral
inflammatory factors. Moreover, this factor indicates
the depletion of the cellular link of immunity in a
continuously recurrent form of larynx papilomatosis
and vice versa, the presence of an inflammatory
potential of lymphocytes in frequently and rarely
recurrent forms of larynx papilomatosis. During
treatment, a decrease in the expression of CD 38+ is
observed, which indicates the presence of an anti-
inflammatory effect of therapy, especially when an IFN
inducer is added to therapy. According to the literature
data, there is information about the role of APO -1/ Fas
(CD95+) receptors in the process of apoptosis, and its
degree is a reflection of the level of lymphocyte
apoptosis. It has been established that an increase in
the expression of CD95+ receptors on lymphocytes
indicates an excessive and inefficient process of
stimulation of blood lymphocytes, which indicates an
apoptotic pathway of lymphocyte death [11]. Thus, a
slightly increased expression of CD 95+ on peripheral
blood lymphocytes was found in groups of children
with laryngeal papillomatosis. It was found that the
highest expression of CD 95+ was typical for children
with a continuously recurrent form of laryngeal
papillomatosis, amounted to 3 2.9±1.3%, and in the
control group 22.4±0.5%. Expression of CD 95+ in other
forms of larynx papilomatosis was intermediate and
did not differ significantly from the values of the
control group ( p>0.05 ). Obviously, excessive
apoptosis in combination with activation of the
humoral link of immunity and deep T-cell
immunodeficiency contributes to the progression of
the disease. During treatment, a decrease in the
Volume 03 Issue 08-2023
33
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
expression of CD95+ is observed. Therefore, the
analysis of activation markers of lymphocytes indicates
a confirmed important role of activation markers of
lymphocytes in the immune response during long-term
viral processes. Thus, the analysis of the results
obtained in laryngeal papillomatosis, depending on the
clinical course of the disease and observation in the
dynamics of treatment, showed that it was possible to
identify pronounced changes both in the cellular link of
immunity, which are manifested by suppression of CD
3 + T-lymphocytes, CD 4 + T - helpers , IRI , an increase
in the number of CD 8 + T-lymphocytes, CD 16 + cells,
and in the humoral immunity - an increase in serum
concentrations of IgG and IgA , increased expression of
CD38+ and CD95+. Moreover, against the background
of standard therapy with the use of IFN, especially with
the use of IFN inducers, there is an improvement in
immunological parameters, which is reflected in a
decrease in the number of relapses of the disease.
It has been established that one of the most important
biological functions of immunoglobulins is antigen
binding and the formation of circulating immune
complexes (CIC) [10] . An important characteristic of
the CEC is their size. It was revealed that with
papillomatosis of the larynx there is an increased
content of circulating immune complexes. There is an
increase in the average CEC values of 3% (large values)
and 4% (small values). We found that the highest
average value of small and large CECs was typical for
patients with a continuously recurrent form of
laryngeal
papillomatosis.
In
other
types
of
papillomatosis of the larynx, there is also a significant
increase in the CEC of small and large. It is known that
CEC 3%, formed with an excess of antibodies, although
they are able to bind complement, are large, insoluble,
rapidly phagocytosed and have low pathogenicity [ 10]
. Soluble immune complexes of small sizes, which were
formed with an excess of antigen, have the greatest
pathological potential [10] . A high level of CEC at can
be due not only to the activation of the immune
response to viral antigens, but also to the suppression
of the mechanisms of their elimination. The latter,
apparently, is associated with a weakening of the
function of cells of the monocyte-macrophage system
- cells that absorb and disintegrate immune complexes
[10,12] . Consequently, there is an activation of the
humoral link of immunity along with a pronounced
depression of the cellular link of immunity. Thus, based
on the results obtained, it can be seen that with a long-
term chronic course with relapses of laryngeal
papillomatosis, a pronounced imbalance of the cellular
and humoral parts of the immune system is observed.
Moreover, the imbalance in the cellular link of
immunity was expressed in the suppression of IRI due
to a decrease in the number of T-helpers/inducers and
an increase in T-cytotoxic lymphocytes. Circulating
immune complexes of large and small values were
increased, however, the greatest increase in the CEC
was observed with a continuously recurrent form of
Volume 03 Issue 08-2023
34
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
laryngeal papillomatosis. Obviously, in this pathology T
- cellular immune response is significantly weak and
directed against a smaller number of epitopes, which
suggests clonal depletion of T-lymphocytes. In turn,
reduced immunoreactivity of the T-cell link in laryngeal
papillomatosis can be considered as a result of a
violation of antigen presentation to immune system
cells, as well as a violation of the function of T-cells
themselves 9 . In the dynamics of treatment, there is
an improvement in the indicators of cellular and
humoral immunity. Especially, pronounced changes
are observed in the group of children taking IFN
inducers in the complex of antiviral therapy, which
contribute to the disclosure of their own potential or
reserve of IFN alpha, beta and gamma, which play an
important role in organizing an adequate antiviral and
antitumor immune response.
Next, we analyzed the results of the analysis of children
with a frequently recurrent form of laryngeal
papillomatosis. The data obtained are presented in
Table 2. On the part of the cellular factors of the
adaptive immune response, when compared with the
data before treatment, it was found that in the group
of children i.e. the 2c group of children was
characterized by an increase in the expression of CD 4+
on lymphocytes by 1.4 times, and in the 2nd group - by
1.2 times, a decrease in the expression of C D 8+ on
lymphocytes in the 2nd group - by 1.4 times, and in 2a
group - 1.1 times, increase in IRI in 2nd group - 1.5 times,
and in group 2a - 1.24 times, CD 38+ decreased in 2nd
group - 1.21 times, and in group 2a - 1.1 times, CD 95+ is
reduced in group 2 - 1.22 times, and in group 2a - 1.1
times, immunoglobulin A is reduced in group 2 - 1.25
times, in group 2a - in 1.2 times; once. The revealed
differences were all significant with the values of the
group before treatment and among themselves.
Table 2.
The immune status of children with laryngeal papillomatosis depending on the clinical features of the disease
(frequently relapsing group) in the dynamics of treatment, M ± m , %
Immunity
parameters
Norm
( n= 29)
Before
treatment
(n= 32 )
Group 2a
(standard + IFN)
( n =25)
Group 2c
(standard + IFN +
inosine
pranobex)
( n =28)
Volume 03 Issue 08-2023
35
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
Leukocytes
6050±128.0
6100±112.7*
7350.5±145.5
7500.0±125.2
Lymphocytes
32.5±0.84
42.5±1.52*
40.2±0.94*^
42.4±1.15*
CD 3+
58.4±1.25
45.7±0.82*
5 1.8 ±1.50*
5 2 .2±0.9* #
CD4+
38.3±1.25
32.6±1.41*
39.40±0.94* ^
44.1±1.23* #$
CD8+
18.8±0.54
32.9±1.15*
29.42±1.42* ^
23.40±1.21* #$
IRI
1.65±0.05
0.92±0.04*
1.14±0.03 *
1.3 8 ±0.0 1*#$
CD 16+ _
18.2 1.0
3 _
21.9±0.24*
20.3± 0.6 0* ^
19.30± 0.84 * #
CD20+
19.9
0.83
2 4.6
1.16 *
2 3, 3
1.1 3*
^
22.1
1.16 *
CD38 + _
22.4±0.86
24.4±1.22*
22, 1 0±1.4 1 *
2 0, 2± 0.96 * $
CD95 + _
23.5±1.26
28.8
1.21*
26.3
0.72*
23.6
0.95* #$
IgG
1260.0
21.60
1341.2±26.2*
1300.4±25.4*
^
1272.0±19.6 #
IgA
122.0
3.21
161.4
2.6*
1 38 .0
2.20 ^
129.4
1.32 #$
IgM
112
2.1
140.4
1.32*
128.61.35 ^ _
_
11 5.4
0.84 #$
CEC3%
8.58±1.34
116.2
2.80
8 2 , 6
1.4 4*
36.5
0.86 #$
CEC4%
14.22±1.51
85.65
2.44*
48.64
0.68 *^
20.54
0.60* #$
Note: * - significance of differences with the data of the control group, ^ - differences of group 2a with values before
treatment; # - differences in group 2 with values before treatment; $ - differences between 2a and 2b groups.
We analyzed the results of the immunological analysis
of children with a rare-recurrent form of laryngeal
papillomatosis. The data obtained are presented in
Table 3. On the part of the cellular factors of the
adaptive immune response , when compared with the
data before treatment, it was found that almost many
values were close to the normal values, however,
significantly different values were found when
Volume 03 Issue 08-2023
36
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
compared with the results before treatment. These
include, against the backdrop of an integrated
approach, i.e. in group 3c, there is an increase in CD 3+
by 1.14 times, an increase in CD 4+ - by 1.14 times, a
decrease in C D 8+ by 1.4 times, an increase in IRI - by
1.4 times, a decrease in CD 38+ and CD 95+, decrease in
immunoglobulin A by 1.2 times, decrease in CIC3% - by
2.6 times, decrease in CIC4% - by 2.2 times. The
differences found were all significant with pre-
treatment group values.
Table 3
The immune status of children with laryngeal papillomatosis in the course of treatment depending on the clinical
features of the disease (rarely relapsing group), M ± m , %
Immunity
parameters
Norm
( n= 29)
Before
treatment
(n= 30 )
Group 3a
(standard + IFN)
( n =24)
Group 3c (standard
+ IFN + inosine
pranobex)
(n= 25 )
Leukocytes
6050±128.0
8200.6±92.5*
7120.5±135.8
6500.3±158.2
Lymphocytes
32.5±0.84
34.2±0.68
33.5±0.84
32.6±1.15
CD3+
58.4±1.25
46.40±0.82*
48.5±1.24*
52.82±1.29 *#$
CD4+
38.3±1.25
34.30±0.68*
36.9±0.84 ^
39.2±0.55 #$
CD8+
18.8±0.54
29.40±0.65*
24.5±0.75* ^
20.5±1.2 #$
IRI
1.65±0.05
0.98±0.03*
1.22±0.04 *^
1.35±0.03 *#$
CD 16+ _
18.2 1.0
3 _
24.2±0.32*
21.20±0.52* ^
20.4±0.25*
CD20+
19.9
0.83
2 3.2
0.86*
2 1.4
0.6
2 0.8
0.22
CD38 + _
22.4±0.86
26.2±1.24*
24.3±0.52*
22.9±0.62 #
CD95 + _
23.5±1.26
28.40
1.12*
24.40
0.38 ^
22.8
1.02 #
IgG
1260.0
21.60
1355.4±23.7
1280.5±1.86*
1265.5±1.99
Volume 03 Issue 08-2023
37
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
IgA
122.0
3.21
146.0
2.94*
134.2
0.92 ^
126.9
1.42 #$
IgM
112
2.1
139.2
0.74
12 4 , 3
2.1 0^
1 19 .5
2, 2 1
CEC3%
8.58±1.34
52.20
0.84
3 1 , 6 0
0, 6 6 ^
19 .8 0
0.58 * # $
CEC4%
14.22±1.51
29.50
1.82*
19.5 5
0.80 *^
13 , 24
0, 48 * #
Note: * - significance of differences with the data of the control group, ^ - differences of group 3a with values before
treatment; # - differences in group 3c with values before treatment; $ - differences between groups 3a and 3b.
CONCLUSION
Thus, unidirectional changes in the state of the immune
response in laryngeal papillomatosis were revealed,
which were most pronounced in the group of children
with a continuously recurrent form of laryngeal
papillomatosis. An etiopathogenetic approach was
used in the treatment of laryngeal papillomatosis in
children, which consisted in the inclusion of an
interferon inducer and licopid in the complex therapy .
Against this background, in addition to improving the
performance of cellular and humoral immunity, there is
an improvement in the clinical condition of children
and a decrease in the frequency of relapses in the
dynamics of treatment of children with laryngeal
papillomatosis. On the part of immunological
parameters, activation of cellular parameters of
immunity, a decrease in activation markers of
lymphocytes and activation of humoral immunity
factors were observed, which indicated the anti-
inflammatory effect of therapy.
REFERENCES
1.
Garashchenko T.I. Study of immunological
parameters in children
with laryngeal
papillomatosis
and
possible
ways
of
immunocorrection // Vestn. otorhinolaryngitis -
1996. - No. 4. - S. 15-18.
2.
Dmitriev G.A. Papillomavirus infection // M.:
Med. book, 2006. - 76 p.
3.
Zaitsev
VS
Clinical
and
morphological
characteristics of papillomatosis of the larynx
in children // Archives of Pathology. 2005. - T.
67, No. 2. - S. 27-29.
4.
Zenger V.G. The current state of the problem of
treating
children
with
respiratory
papillomatosis.
Bulletin
of
Otorhinolaryngology. 2000. - No. 4. - S. 17-21.
5.
Ivanova M.A. The incidence of sexually
transmitted
infections
in
the
Russian
Federation: 2002-2004 // Clin.dermatol. and
venerol. 2005. - No. 4. - S. 9-12.
6.
Ivanchenko G.F. Modern ideas about the
etiology, pathogenesis, clinic, diagnosis and
Volume 03 Issue 08-2023
38
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
08
P
AGES
:
25-38
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
treatment of laryngeal papillomatosis // Vestn.
otorhinolaryngitis 2000: - No. 1. - S. 44-48.
7.
Karimova F.S. Treatment of papillomatosis of
the larynx with interferon inducers // Materials
on the effectiveness of the use of cycloferon in
the clinic of ENT diseases. St. Petersburg:
"Taktik-Studio", 2006. - S. 49-52.
8.
Mezentseva M.V. Patterns of functioning and
directed correction of the cytokine regulatory
network: Ph.D. dis. doc. biologist, science. /
M.V. Mezentsev. Moscow, 2006. - 32 p.
9.
Novikov D.K., Vykhristenko L.R. et al.
Immunology and allergology for JIOP doctors //
M.: Med. information agency, 2006. -512 p.
10.
Pluzhnikov M.S., Katinas E.B., Ryabova M.A.
Clinical and immunological characteristics of
recurrent respiratory papillomatosis // Ros.
otorhinolaryngitis 2006. - V. 22, No. 3. - S. 22-26.
11.
Pluzhnikov M.S. Immunotropic therapy in ENT
practice // Handbook of immunotherapy for
practice. doctor. SPb., 2002. - S. 392-401.
12.
Sidorenko S.I. Interferon preparations and its
inducers in the complex therapy of juvenile
respiratory papillomatosis: Ph.D. dis. cand.
honey. Sciences. M., 2001. - 21 p.
13.
Soldatsky Yu.L. Adjuvant therapy of recurrent
respiratory papillomatosis in childhood //
Pediatrician. pharmacol. - 2006. - No. 2. - S. 26-
30.
14.
Soldatsky Yu.L. Diseases of the larynx //
Pediatrician, Pharmacol.: scientific-practical.
Journal of the Union of Pediatricians of Russia.
2008. - Volume 5; No. 3. -S. 28-31.
15.
Tapilskaya N.N. The use of viferon in the III
trimester of pregnancy for the prevention of
infection
of
newborns
with
human
papillomavirus // Terra Medica. 2006. - No. 4. -S.
15-17.
16.
Craig C. , MD. Derkay. Craig S. Recurrent
respiratory papillomatosis // Laryngoscope.
2001. - Vol. 111. - P. 57-69.
17.
Goon R ., Sonnex C ., Jani R . et al. Recurrent
respiratory papillomatosis: an overview of
current thinking1 and treatment // Eur Arch
Otorhinolaryngol. 2008.265(2).-P. 147-151.
18.
McKenna M. Extraesophageal acid reflux and
recurrent respiratory papilloma, in children / M.
McKenna, L. Brodsky // Int J Pediatr
Otorhinolaryngol. 2005. - Nk 69. - P. 597-605
PubMed.