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Chlamydia trachomatis infection
Introduction:
Chlamydia trachomatis is an obligate intracellular gramnegative like
bacterium and an important cause of sexually
transmitteddiseases
worldwide (de Muylder et al., 1990; Ville et al., 1991; den
Hartog
et al., 2005). Many chlamydial infections are asymptomatic, and
re-infections are common. If left untreated, Chlamydia has a
high tendency
to remain persistent in inflamed tissues of the upper genital
tract of patients with pelvic inflammatory disease (Cohen and
Brunham, 1999; den Hartog et al., 2006). Prolonged
inflammation
may lead to tissue scarring and occlusion of Fallopian tubes.
Although
many women are infected with C. trachomatis, only a minority
will
develop tubal factor infertility. Moreover, a clearance rate of
44.7%
has been reported in asymptomatic and untreated women after 1
year follow-up (Morre et al., 2002). These results imply that
host
genetic factors play an important role in modulating the immune
defence mechanisms and thereby determining the pathogenesis
of
chlamydial diseases. However, the genetic basis underlying this
phenomenon has remained unclear.
Genes involved in the immune response appear ideal candidates
for
further study, given their function and polymorphism, as well as
data
from previous studies (Cohen et al., 2000, 2003; Kinnunen et
al.,
2002). It has been found that, after C. trachomatis infection,
downregulation
of the major histocompatibility complex (MHC) class I is
one of the mechanisms C. trachomatis-infected cells use to
evade an
immune response involving recognition and destruction by
cytotoxic
T lymphocytes (Zhong et al., 2000). However, the downregulation
of MHC class I leads to activation of natural killer (NK) cells
because of a decreasing inhibitory signal generated by the
binding of
inhibitory receptors to their ligands Simultaneously, the NK
cell-activating ligands, such as major histocompatibility
complex class
I chain-related A (MICA), may be up-regulated. Through t
interaction between the activating ligands
and their corresponding
receptors, the activating signals of the NK cells increase.
Moreover, one of the most relevant cytokines involved in the
response against C. trachomatis is interferon-g (IFN-g)
(Srivastava
et al., 2008). One of the most important sources of IFN-g is
from
NK cells. Stimulation of NK cells by the NKG2D receptor by
means
of its ligand, MICA, results in the release of the cytokine IFN-g
(Bauer et al., 1999)). We therefore believe that the relationship
between polymorphism of the MICA ligand and susceptibility to
C. trachomatis infection deserves further study.
The MICA genes are situated 46 kb upstream of human
leucocyte
antigen B and encode a stress-inducible molecule with three
extracellular
domains (a1, a2 and a3), a transmembrane region and a
cytoplasmic
tail. Its domain structure is similar to MHC class I antigens
without b2-microglobulin (Bahram et al., 1994; Tieng et al.,
2002).
Like MHC class I genes, the MICA locus is highly polymorphic,
with
at least 53 alleles having been described.
At present, the role of MICA polymorphisms has not been
investigated
either in the susceptibility to the development of tubal pathology
or in C. trachomatis-associated tubal factor infertility. Therefore,
the
first objective of our study was to assess whether
polymorphisms of
MICA genes are associated with tubal pathology by comparing
Serology
Chlamydial antibody testing is a routine procedure in the
fertility workup.
Peripheral venous blood was collected for the analysis of IgG
antibodies
against C. trachomatis using commercially available enzyme
immunoassay
kits (Immuno-Biological Laboratories, Minnesota, USA). The
results
were obtained in terms of the mean absorbance (optical density,
OD)
at 450 nm. The antibody index of each determination was
calculated by
dividing the OD value of each sample by the cut-off value.
Positive
C. trachomatis specific IgG results were defined as antibody
index .1.1,
as recommended by the manufacturer. Samples with grey zone
values,
e.g. 1.0+0.1, were repeated and considered positive when the
resul
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Submitted on May 17, 2009; resubmitted on July 21, 2009; accepted
on August 27,
2009
MICA alleles and Chlamydia trachomatis 3095
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