JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2007, 58, Suppl 5, 117–127
www.jpp.krakow.pl
U. DEMKOW
1, 2
, M. FILEWSKA , D. MICHALOWSKA-MITCZUK , J. KUS ,
1
1
1
J. JAGODZINSKI , T. ZIELONKA , Z. ZWOLSKA , M. W¥SIK ,
3
1
1
2
E. ROWINSKA-ZAKRZEWSKA
1
HETEROGENEITY OF ANTIBODY RESPONSE
TO MYCOBACTERIAL ANTIGENS IN DIFFERENT CLINICAL
MANIFESTATIONS OF PULMONARY TUBERCULOSIS
1
Institute of Tuberculosis and Lung Diseases, Warsaw, Poland;
2
Department of Laboratory
Diagnostics and Clinical Immunology of the Developmental Age, Warsaw Medical University,
Warsaw, Poland;
3
Tuberculosis and Lung Diseases Center, Otwock, Poland
Different clinical outcomes of tuberculosis can be related to the balance between
cell-mediated and humoral immunity. In this prospective study we examined the
humoral immune responses to recombinant and native mycobacterial antigens in
relation to clinical presentations of pulmonary TB. Two hundred and fifteen serum
samples were examined including: non-cavitary (n = 120), cavitary (n= 65), caseous
pneumonia (n=12), and disseminated TB (n=18). ELISA tests detecting IgG, IgA,
and IgM against antigens: 38kDa and 16kDa, 38kDa and lipoarabinomannan (LAM)
were used. Univariate and multivariate logistic regression analyses were carried out
to find the association between the antibody level and demographic or clinical
characteristics. The relationships among specific antibody profiles and the phase of
the disease in relation to demographic (age and sex) and clinico-radiological factors
were investigated by measuring serum antibody levels (IgG, IgA, and IgM) to 38kDa
and 16kDa recombinant M. tuberculosis antigens and to LAM – native mycobacterial
antigen. The results show that the radiological extent of the disease is the strongest
factor
associated
with
IgG
antibody
production.
Patients
with
more
extensive
pulmonary TB showed higher titers of IgG antibody to M. tuberculosis antigens
(P<0.0001). The highest IgG and IgA level were observed in fibro-cavernous TB.
The presence of cavity was associated only with IgG anti 38+16kDa (P<0.001). IgA
level was the highest in caseous pneumonia. IgM antibody production was not
associated with any clinical and radiological factor, but only with the male gender.
Age was independently and inversely associated with IgG anti 38kDa+LAM level
and IgM anti 38kDa+LAM. We conclude that the humoral immune response to
mycobacterial antigens is highly heterogeneous and varies with the stage of TB. IgG
antibody level is higher in most advanced and extensive forms of the disease.
Key
words:
humoral immune response, mycobacterial antigens, tuberculosis
118
INTRODUCTION
M. tuberculosis infection presents in various clinical forms, ranging from
asymptomatic lifelong infection to multibacillary disseminated disease (1, 2).
Within the framework of contemporary immunology, different patterns of the host
response suggest the existence of a broad spectrum of immune reactions to M.
The
tuberculosis.
spectrum
of
TB
is
compared
to
leprosy,
with
an
inverse
relationship between the antibody and T-cell immunity (2-5). At one pole of the
spectrum,
in
self-limiting
disease,
patients
mount
a
strong Th1 type
immune
response and localize the infection (3-5). At the opposite pole, in disseminated
form,
there
is
diminished
cell-mediated
immunity and
augmented
antibody
response, which results in failure to restrict the growth of the pathogen (4-6).
However, in human TB the striking correlation between the ability to generate the
cell-mediated immune response and to restrict the growth of M. tuberculosis has
not been established.
Although
the
immunity
to
TB
is
cell-mediated,
humoral
responses
are
common (4-7). The dogma has been that the antibody response is unimportant for
TB immunity and pathogenesis (7). The inability of various investigators to
generate
effective
sera
in
prevention
and
treatment
of
TB
infection
was
an
important contributor to today’s belief that the antibody-mediated immunity plays
a minor or negative role in the outcome of TB infection (7). However, majority
of published experiments with the use of serum therapy for TB did produce some
evidence of the efficacy of the serum against M. tuberculosis (7). Unfortunately,
lack of appropriate controls, minimal descriptions in many studies, and unknown
antibody
levels
make
a
large
part
of
the
experience
with
serum
therapy
inconclusive in regard to the role of antibody in protection against TB (7).
The knowledge of the humoral immune responses at various stages of TB
infection and disease could help elucidate the complex interaction between the
host and the pathogen (4-7). A comprehensive immune profiling of antigenspecific responses in relation to clinical phase of the disease is critical not only to
the understanding of disease pathogenesis, but this knowledge can be used for
diagnostic purpose. Therefore, in the present study we attempted to correlate the
type and intensity of the humoral immune response to mycobacterial antigens
with different clinical manifestations of pulmonary TB.
MATERIAL AND METHODS
Patients and tuberculosis status
Serum samples from 215 subjects with pulmonary TB (78 females and 137 males) were
examined. The mean age of the examined group was 44.7 years (range 19-90 years). TB patients
were
referred
to
the
Institute
of
Tuberculosis
and
Lung
Diseases
in
Warsaw,
Poland
and
Tuberculosis and Lung Diseases Center in Otwock, Poland. All subjects gave informed consent for
participation in the study and the study protocol was approved by a local Ethics Committee. All
119
patients were Caucasian, HIV negative, and previously BCG vaccinated. Patients were classified
into four groups depending on the results of clinical and radiological findings: (1) 120 cases of noncavitary infiltrative TB, (2) 65 cases of cavitary disease, (3) 12 cases of caseous pneumonia and
(4)18 cases of disseminated TB (miliary TB). According to the radiological extend of the disease,
all patients were also categorized into 3 groups: minimal changes (disease limited to 1 lobe) (n=78),
moderate changes (bilobular changes) (n=68), and advanced disease (changes in 3 or more lobes)
(n=69). All patients with advanced disease had bilateral disease or miliary TB. All cases represented
postprimary
form
of
tuberculosis.
The
group
examined
included
150
new
cases
(duration
of
symptoms shorter than 6 months), 51 chronic cases with multidrug resistant TB, and 68 cases of
recurrent TB. Recurrent TB was defined as the confirmed TB episode 6 months or more after the
completion of previous antituberculous therapy that was considered successful. The diagnosis was
confirmed by sputum culture in 133 from new and recurrent cases and in all (n=51) chronic cases.
The examination of acid-fast bacilli was made using Ziehl-Neelsen stain, culture on LöwensteinJensen solid egg-based medium or by Bactec system. In 12 patients, the diagnosis was confirmed
by
histological
testing
(evidence
of
caseating
granulomas
in
pleural
biopsy
specimen).
In
19
patients, TB was diagnosed by panel decision on the base of suggestive clinico-radiological signs
(in the absence of evidence for alternative infective or non-infective process), tuberculin skin test,
and reevaluation after specific antituberculous treatment. The evidence of pleural tuberculosis was
present in 14 patients. A hundred and eighty three patients did not receive antituberculous treatment
at the time of blood collection, and in the 32 remaining cases the duration of therapy was shorter
than 1 month. Six patients received oral corticosteroids (pleural involvement, disseminated TB).
Methodology
Blood samples were collected, centrifuged, and the serum was stored at -40°C until use. An
array of commercial immunoenzymatic kits to detect IgG antibodies against 38kDa plus 16kDa
(Pathozyme tb complex plus, Omega Diagnostics, Scotland) and IgG, IgA, and IgM antibodies to
38kDa
plus
lipoarabinomannan
(LAM)
(MycoG,
MycoA,
and
MycoM,
Omega
Diagnostics,
Scotland) was applied. 38kDa and 16kDa are recombinant mycobacterial antigens expressed in and
purified from E. coli. LAM is a native mycobacterial antigen. All tests are based on a solid double
antibody sandwich ELISA. Sera diluted 1:50 or 1:100 (according to the manufacturer’s instruction)
were added to microwells precoated with antigens. All samples were assayed in duplicates. In the
positive cases, antigen-antibody complex reacted with peroxidase-labeled antihuman IgG (IgA or
IgM) conjugate. Using H2O2/TMB as substrate, the enzymatic activity of peroxidase was measured
at 450 nm with the use of automated reading system ELX 800 (Biotec). All the results except for
IgM tests were referred to the standard curve. The standards were provided for the generation of a
semi-logarithmic reference curve. As the sera were diluted 1:50 or 1:100, the units extrapolated
from the standard curve were multiplied by 50 (100) to obtain sero-units for the result interpretation.
Results of IgM tests were expressed as the ratio of optical density (OD) of the examined sample to
the OD of a cut-off sample.
Statistical analysis
Results of antibody titers were compared by analysis of variances (ANOVA). Univariate analysis
and multivariate regression logistic analysis were performed to analyze variables that might have
influenced the humoral immune response to the examined antigens. All variables of the same
category that were significant in the univariable analysis were compared with the use of the Tukey
multiple comparison test for pairwise comparisons. Statistical significance was accepted at a level of
P<0.05. All variables whose changes appeared significant by univariate analysis were subjected to
120
the multivariable analysis. Results of multivariate analysis (all categories together) are expressed as
adjusted regression coefficients (CR) with their associated 95% confidence intervals (CI). Nonsignificant variables were eliminated. All analyses were performed with S-PLUS 2000 (8).
RESULTS
In univariate analysis, the IgG response to 38+16kDa was associated with:
culture positive TB, chronic TB, fibro-cavernous or disseminated disease, and the
presence of the cavity and extensive radiological changes. In the culture positive
cases, the mean antibody level was 437.15 U/ml and in the culture negative cases
- 163.21 U/ml (P<0.001). The mean antibody level in new cases was 313.97
U/ml, in chronic cases – 775.19 U/ml, and in recurrent disease – 334.47 U/ml.
The
difference
between
new
and
chronic
cases
was
statistically
significant
(P<0.001). The mean antibody levels in different clinical presentation of the
disease were the following: infiltrative TB – 312.64 U/ml, disseminated TB –
640.15
U/ml,
caseous
584.47
U/ml.
Statistical
pneumonia
–
differences
218.68
between
U/ml,
fibro-cavernous
infiltrative
and
disease
disseminated
–
or
fibro-cavernous form were significant (P<0.001). In the patients with radiological
changes limited to 1 lobe, the mean antibody level was 91.71 U/ml, with bilobular
changes – 424.82 U/ml, and with extensive changes – 674.79 U/ml. All groups
Fig.1. Mean
level (±SD)level
in relation
examined
Fib-cav
– fibrocavernous
TB, Pneu
Fig.IgG
1. anti-38+16kDa
Mean IgG anti-38+16kDa
(±SD)toin
relation factors.
to examined
factors.
Fib-cav –
cas – pneumonia
caseosa,
TB, Infiltr
– –infiltrative
TB;TB,
Hist
– diagnosis
confirmed by
fibrocavernous
TB,Dissem
Pneu cas––disseminated
pneumonia caseosa,
Dissem
disseminated
Infiltr
– infiltrative
histological
testing,
Clin/rtg –confirmed
diagnosisbyon
the base testing,
of clinico-radiological
criteria,
– of
culture
positive TB;
TB;
Hist – diagnosis
histological
Clin/rtg – diagnosis
on theBA
base
clinicoRecurr – radiological
recurrent TB,
Chronic
cases, New
– new –cases;
1 areas
– 1 lobe–involvement,
criteria,
BA –
– chronic
culture positive
TB; Recurr
recurrent
TB, Chronic
chronic cases,2 areas – 2
lobes involvement,
areas1 –areas
3 and
lobes involved;
Caverna
Yinvolvement,
– cavitary TB,
Caverna
Nmore
– non-cavitary
New – new 3
cases;
– 1 more
lobe involvement,
2 areas
– 2 lobes
3 areas
– 3 and
TB; M - men,
- women.
lobesW
involved;
Caverna Y – cavitary TB, Caverna N – non-cavitary TB; M - men, W - women.
121
differed significantly (P<0.0001). In the cavitary form, the antibody level was
543.46 U/ml and in the non-cavitary form - 192.96 U/ml (P<0.001). These results
are presented in Fig. 1.
The IgG response to anti-38kDa+LAM was associated with the phase of the
disease and its radiological extent. The mean antibody level in infiltrative TB was
331.77 U/ml, in disseminated form – 140.60 U/ml, in caseous pneumonia –
885.14 U/ml, and in fibro-cavernous TB – 620.27 U/ml. The difference between
infiltrative and fibro-cavernous disease was statistically significant (P=0.003).
The mean antibody level in the group with minimal radiological changes was
247.27 U/ml, with moderate changes - 444.35 U/ml, and with extensive changes
– 612.29 U/ml. The difference between the groups with minimal and extensive
changes
was
significant
(P<0.01)
(Fig.
2).
IgG
anti-38kDa+LAM
level
was
inversely correlated with age (P<0.001) (data not shown).
The IgA anti-38kDa+LAM response was associated only with the radiological
extent of TB: 1 lobe changes – 340.19 U/ml, bilobular – 864.21 U/ml, and
extensive
changes
–
798.12
U/ml.
The
difference
between
the
groups
with
minimal and extensive changes was significant (P=0.02) (Fig. 3).
The
production
of
IgM
anti-38kDa+LAM
was
associated
only
with
the
gender. The mean OD index in the group of men was 0.72 and in group of women
was 1.09 (P=0.02) (Fig. 4). IgM anti-38kDa+LAM was also negatively correlated
with age (P<0.01) (data not shown).
On the basis of multivariate logistic regression, independent factors associated
with the humoral response to specific antigens were identified. The results are
presented
as
adjusted
regression
coeficients
(CR)
with
their
associated
95%
Fig. 2. Mean
IgG
anti-38kDa+LAM
level (±SD)
in relation
to the to
examined
factors.
Abbreviations
as in Fig. 1.
Fig. 2.
Mean
IgG anti-38kDa+LAM
level (±SD)
in relation
the examined
factors.
Abbreviations
as in Fig. 1.
The production of IgM anti-38kDa+LAM was associated only with the gender. The mean
OD index in the group of men was 0.72 and in group of women was 1.09 (P=0.02) (Fig. 4).
IgM anti-38kDa+LAM was also negatively correlated with age (P<0.01) (data not shown).
On the basis of multivariate logistic regression, independent factors associated with the
humoral response to specific antigens were identified. The results are presented as adjusted
122
Fig. 3.
Mean
IgA anti-38kDa+LAM
level in
(±SD)
in relation
to the examined
Abbreviations
Fig. 3. Mean
IgA
anti-38kDa+LAM
level (±SD)
relation
to the examined
factors.factors.
Abbreviations
as in Fig. 1.
as in Fig. 1.
Fig. 4. Mean
optical density index (±SD) of IgM anti-38kDa+LAM measurement in relation to the examined
Fig. 4. Mean optical density index (±SD) of IgM anti-38kDa+LAM measurement in relation to the
factors. Abbreviations
as in Fig. 1.
examined factors. Abbreviations as in Fig. 1.
The radiological extent of changes was associated with the IgG level anti-38+16kDa
confidence
(CI).P<0.01,
Results higher
than 1
indicate
that the
category selected
(bilobular
changesintervals
- CR=2.15,
3 or more
lobes
involved
- CR=4.66,
P<0.001) and
presents
with38kDa+LAM
a higher mean(bilobular
antibody level
than -the
reference
category.
Results
with the
IgG anti
changes
CR=1.6,
P=0.04,
3 or
more lobes
lower
than 1 indicate
an The
inverse
relationcategory
between was
the categories
compared.
involved
- CR=4.66,
P<0.01).
reference
taken as the
disease limited to 1
radiological
changes was
was independently
associated with associated
the IgG level
lung lobe.The
Clinical
courseextent
of theof disease
withantiIgG anti38+16kDa
(bilobular
changes
CR=2.15,
P<0.01,
3
or
more
lobes
involved
38+16kDa (category chronic cases - CR= 2.36, P<0.05); the reference category being
new
CR=4.66,
P<0.001)
and
with
the
IgG
anti
38kDa+LAM
(bilobular
changes
cases. Radiological presentation of the disease was associated with IgG anti 38kDa+LAM
antibody level (fibro-cavernous - CR= 1.98, P<0.02) and IgA anti-38kDa+LAM (caseous
pneumonia - CR= 4.13, P<0.01); the reference category being infiltrative TB. The male
gender was independently associated with lower IgM level (CR=0.71, P<0.01). Age was
independently associated with IgG anti-38kDa+LAM level (CR=0.98, P<0.001) and IgM
anti-38kDa+LAM (CR=0.99, P=0.04). The correlation was negative in both situations. Fig. 5
123
5. Factors
independently
associated
the humoral
immune
response
to specific
antigens.
.
Fig. 5.Fig.
Factors
independently
associated
with with
the humoral
immune
response
to specific
antigens
CR=1.6, P=0.04, 3 or more lobes involved - CR=4.66, P<0.01). The reference
DISCUSSION
category was taken as the disease limited to 1 lung lobe. Clinical course of the
disease was independently associated with IgG anti-38+16kDa (category chronic
It
is generally accepted that the immune response to M. tuberculosis is biphasic, with the
- CR= 2.36, P<0.05); the reference category being new cases. Radiological
IFN-cases
cellular
response detected early and IL-4 driven antibody response detected late in the
presentation of the disease was associated with IgG anti 38kDa+LAM antibody
course of infection (9-11). In the present study, the humoral immune response to the M.
level (fibro-cavernous - CR= 1.98, P<0.02) and IgA anti-38kDa+LAM (caseous
antigens at different stages of disease was evaluated. The relationships between
tuberculosis
pneumonia - CR= 4.13, P<0.01); the reference category being infiltrative TB. The
the specific
antibody profiles and the phase of the disease and in relation to demographic (age
male gender was independently associated with lower IgM level (CR=0.71,
and sex)
and clinico-radiological factors (culture status, radiological extent, clinical form of
P<0.01). Age was independently associated with IgG anti-38kDa+LAM level
the disease,
etc) was investigated by measuring the serum antibody levels (IgG, IgA, and
(CR=0.98, P<0.001) and IgM anti-38kDa+LAM (CR=0.99, P=0.04). The
IgM) to 38kDa and 16kDa recombinant M. tuberculosis antigens and to LAM-native
correlation was negative in both situations. Fig. 5 presents the results of
mycobacterial antigen.
multivariate analysis. These results are expressed as a relative risk. Lower and
Age was independently and inversely associated with the IgG anti-38kDa+LAM and IgM
higher limits of each variable determine the confidence interval.
anti-38kDa+LAM levels. IgM antibody is the first to appear in response to any antigen and
therefore could be expected to be high in recent TB and to decline in most advanced phases as
a result of longer duration of infection in older age (12). Epidemiological data from Poland
confirm that the incidence of TB is higher in older age groups. A decline of IgG antibodies
generally
accepted
that of
the
to M.
is
with ageItisisprobably
related
to aging
theimmune
immuneresponse
system (12).
It istuberculosis
probably dependent
on
biphasic,
withimpairment
the IFN-γ cellular
response
detected
early
and IL-4
driven antibody
T-helper
function
in older
age, resulting
from
thymic
involution
(12). A deficit of
response
late
in the course
(9-11).
In the
present
study, the
T helper
cellsdetected
leads to
impairment
of ofB infection
cell function
and
lower
production
of specific
humoral
immune
response
the1.4
M. time
tuberculosis
antigens
different
stages
of
antibodies
(12).
The IgM
level towas
higher in
womenat than
in men.
That
may be
disease was evaluated. The relationships between the specific antibody profiles
related to different clinical presentations of the disease in either gender, but this kind of
and the phase of the disease and in relation to demographic (age and sex) and
analysis
was not performed in the present study. On the other hand, IgM antibody production
(culture status, radiological extent, clinical form of
was clinico-radiological
not associated withfactors
any clinical
and radiological factor, as opposed to IgG and IgA
the disease, etc) was investigated by measuring the serum antibody levels (IgG,
production. Several authors suggested that IgM are produced mainly in the early phase of
primary TB infection (13, 14). We were not able not confirm this observation as most of our
patients presented with post-primary form of the disease. In our study, the early and late
phases of post-primary TB did not differ with respect to the IgM production. It is known that
the IgM synthesis is regulated by different mechanisms than those responsible for synthesis of
other classes of immunoglobulin, which are generally T-cell independent. IgM
DISCUSSION
124
IgA, and IgM) to 38kDa and 16kDa recombinant M. tuberculosis antigens and to
LAM-native mycobacterial antigen.
Age was
independently
and
inversely
associated
with
the
IgG
anti-
38kDa+LAM and IgM anti-38kDa+LAM levels. IgM antibody is the first to
appear in response to any antigen and therefore could be expected to be high in
recent TB and to decline in most advanced phases as a result of longer duration
of infection in older age (12). Epidemiological data from Poland confirm that the
incidence of TB is higher in older age groups. A decline of IgG antibodies with
age is probably related to aging of the immune system (12). It is probably
dependent on T-helper function impairment in older age, resulting from thymic
involution (12). A deficit of T helper cells leads to impairment of B cell function
and lower production of specific antibodies (12). The IgM level was 1.4 time
higher
in
women
than
in
men.
That
may
be
related
to
different
clinical
presentations of the disease in either gender, but this kind of analysis was not
performed in the present study. On the other hand, IgM antibody production was
not associated with any clinical and radiological factor, as opposed to IgG and
IgA production. Several authors suggested that IgM are produced mainly in the
early phase of primary TB infection (13, 14). We were not able to confirm this
observation as most of our patients presented with post-primary form of the
disease. In our study, the early and late phases of post-primary TB did not differ
with respect to the IgM production. It is known that the IgM synthesis is regulated
by different mechanisms than those responsible for synthesis of other classes of
immunoglobulin, which are generally T-cell independent. IgM antimycobacterial
antibodies may be influenced by environmental factors, such as BCG vaccination,
contact with environmental mycobacteria, or even the presence of latent TB
infection (14).
In the present study, several associations between the type and intensity of the
humoral immune response to mycobacterial antigens and different manifestations
of pulmonary TB were found. Chronic tuberculosis was positively associated with
IgG
anti
38+16kDa
compared
with
new
TB
cases.
This
observation
can
be
explained by a long-term stimulatory effect and intensity of stimulation in chronic
cases. Chronic TB patients are usually non-compliant, with multidrug resistant
disease, irregularly treated. Several patients from the examined group died in the
course of drug resistant TB. It is possible that an increased antigenic load in this
group
of
patients
caused
persistent
and
intensive
stimulation
of
antibody
production along with suppression of the cellular arm of the immune response.
We found no data in the literature concerning the humoral immune response in
chronic TB patients. In the present study, IgG antibody titer was higher in culture
positive groups. This observation was confirmed by others (14, 15). Although the
IgG level was higher in culture positive groups, compared with culture negative
ones, the culture status surprisingly had no independent impact on the serologic
response. The strongest factor independently associated with the intensity of
antibody production was the radiological extent of TB changes. This concerned
125
both IgG and IgA-based tests. The humoral IgG response was highest in most
extensive radiological cases, but the difference between the group with minimal
changes (1 lobe involvement) and the group with moderate changes (2 lobes) was
also
highly
38+16kDa
significant.
and
IgG
The
humoral
immune
anti-38kDa+LAM
was
response
more
then
based
4
on
times
IgG
anti-
stronger
in
advanced compared with the minimal TB changes group. Similar observations
have been noted by other authors (14, 16-18). Radiological extensiveness of the
disease is the strongest factor associated with antibody production. Progress of
the disease in most advanced forms may result from diminished local cellular
response.
An
impairment
of
T-cell
function
leading
to
dissemination
of
the
disease is also observed in immunosuppressed patients. However, in such cases a
weak T-cell response is also connected with deficient antibody production. An
augmented humoral response may accompany slow, long-term progression of the
disease in untreated immunocompetent patients. In such situations, IgG and IgAbased immune response is pronounced in parallel with persistent stimulation due
to increasing antigenic load. Progression of the disease may also be explained by
the hypothesis of polarization of immune response, causing a shift toward the
humoral arm that is not able to combat the disease (19). This is an open question
if such imbalance is a primary phenomenon followed by the progression of the
disease, or the other way around. A correlation between antibody production and
infection stage together with genetic background was found in animals infected
with
M.
tuberculosis
(15-17,
19).
In
the
present
study,
selected
radiological
presentations of the disease were associated with IgG and IgA, but not with IgM,
production. The IgG and IgA levels were lowest in infiltrative TB compared with
all other examined presentations. The highest IgG and IgA levels were observed
in fibro-cavernous TB, which is an advanced, post-primary form of the disease.
Similar findings have been reported by other authors (14, 15, 18). Increased
production of IL-4 in TB patients has been observed in individuals with advanced
involvement of lung parenchyma, with high bacterial loads in sputum (20). In our
study, the presence of cavity was associated only with IgG anti-38+16kDa. This
may be due to the fact that in this group there were patients with advanced (fibrocavernous TB) and also those with an early form of TB (infiltrative TB with
necrosis). These results suggest that an alteration in type 1 and type 2 cytokine
balance can occur in TB patients being in advanced clinical stage.
The clinical spectrum of TB is related directly to the strength of activation of
various arms of the immune system. Patients with self-limiting TB show strong
T cell reactivity, while patients with the disseminated form of the disease present
an
augmented
antibody
response.
IgG
antibodies
(interleukin
4-dependent)
correlate best with clinical and radiological stage of the disease. Patients with
more extensive pulmonary tuberculosis showed higher titers of IgG antibody to
M. tuberculosis antigens. IgG antibodies to 38 kDa antigen are elicited during the
advanced
stage
of
the
disease
(21,
23).
The
Th1-type
immune
response
is
believed to be necessary for protection against mycobacterial pathogens, such as
126
Mycobacterium tuberculosis (5, 6, 21). These facultative intracellular pathogens
reside in mononuclear cells, which allow them to escape the immune response of
the host. Therefore, there is a crucial requirement for a coordinated cellular
immune response to control the infection. Humoral immunity is strong only in the
presence
of
large
numbers
of
microorganisms
and
vary
depending
on
the
specificity of the antibodies. Early tuberculosis and advanced tuberculosis are
characterized by different antibody profiles. It indicates that the targets of the
immune
response
duration
of
are
infection
related
(22-24).
to
the
tuberculosis
Further
insights
state
into
and
the
the
origin
intensity
of
the
and
unique
immune spectrum in TB require a detailed analysis of the cellular and humoral
immune mechanisms.
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Author’s address: U. Demkow, Department of Laboratory Diagnostics and Clinical Immunology
of the Developmental Age, Warsaw Medical University, Banacha 1a St., 02-097 Warsaw, Poland;
phone: +48 22 5991000; e-mail: [email protected]