Journal of Mosquito Research, 2013, Vol.3, No.1, 1-10
ISSN 1927-646X
http://jmr.sophiapublisher.com
5
C4, factor B), 21-hydoxylase, and tumor necrosis
factors (TNFs) (Choo, 2007). Proteins produced by
HLA class
?
have function for the inflammatory
process or other immune system activity (Panchal et
al., 2012). Several SNPs found in the regulatory
region influence transcription of TNF-a gene and
circulating level of TNF-a and thus increases the
susceptibility to human diseases including viral
diseases (Qidwai and Khan, 2011; Tumangger and
Jamil, 2010). A study found that TNF-a was able to
increase endothelium cell (EC) permeability
in vitro
,
which suggests its possible role in DHF pathogenesis
(
Dewi et al., 2004). In an animal model of
DENV-induced hemorrhage study, Chen et al (2007)
found that there was correlation positive between
TNF-a levels in several tissues and EC apoptosis
and hemorrhage. In addition, TNF-a level has been
shown to be high in sera of DENV infected mice
(
Atrasheuskaya et al., 2003). A clinical study found
that high TNF-a concentration was correlated with
thrombocytopenia among dengue infection patients
(
Bozza et al., 2008). Another study found that plasma
levels of TNF-a is significantly higher in DHF than in
DF (Chakravarti and Kumaria, 2006).
Harapan et al (2013) stated that TNF-a is associated
with DHF/DSS development by many pathways
including: (a) TNF-a is a potent EC activator
therefore it enhances permeability of capillary; (b)
TNF-a induces EC to produce reactive nitrogen and
oxygen species and induces apoptotic cell death;
(
c)TNF-a induces tissue factors gene expression on
monocytes and EC; (d) TNF-a represses
thrombomodulin gene expression on EC; (e) TNF-a
effect IL-6 production directly, therefore TNF-a effect
coagulation and fibrinolysis; and (f) TNF-a mediates
in peripheral T-cell deletion.
Interestingly, Loke et al (2002) found no association
between
TNF-a
–238
G/A
and
–308
G/A
polymorphisms and DHF in Vietnamese patients.
However, other study in a Venezuelan study,
Fernandez-Mestre et al (2004) confirmed that the
TNF-a –308 variant allele more frequent found in
DHF compared with DF patients. Fernandez-Mestre et
al (2004) documented an association between TNF-a
–308
A allele in DF patients with hemorrhagic
manifestations, suggesting this variant allele as a
possible risk factor for bleedings in DENV infection.
In other study, the TNF-a –238A polymorphism
combined with lymphotoxin-alpha (LTA)-3 haplotype
were correlated significantly with DHF compared with
DF (Vejbaesya et al., 2009). More recently, Perez et al
(2010)
confirmed that the allele distribution of TNF-a
promoter polymorphism revealed the association of
allele A (high production of TNF-a) to DHF
significantly in Cuba. A higher frequency of carriers
of genotype –308GG (low production of TNF-a) was
observed in controls, whereas the DHF group showed
a major distribution of AA and AG genotypes (high
production of TNF-a). However, the association
between genotype AA and DHF was not significant.
2.4
HLA-Related Proteins
2.4.1
Mayor Histocompatibility Complex (MHC)
class I chain-related protein A and B (MICA and
MICB)
MICA and MICB genes, member of the MIC family,
have an open reading frame and encode cell surface
expressed molecules (Bahram, 2000; Kennedy et al.,
2002).
MICA is stress-induced antigens that are
recognized by cytotoxic T cells and natural killer cells
(
Lanier, 2000). MICA has critical role in the
surveillance of transformed infected and damaged
cells. The MICA gene has been identified as 46.4 kb
located on on the short arm of human chromosome 6
(
Kennedy et al., 2002). Previous studies have
demonstrated polymorphic (GCT)n triplet repeats in
the transmembrane region of the MICA gene,
designated A4, A5, A6, A9, and A5.1, representing
four, five, six, and nine copies of (GCT), and
(
GCT)4(GGCT), respectively (Cheng et al., 2000;
Kennedy et al., 2002). MICB molecules are ligand of
NKG2D receptors on NK cells, gamma/delta T cells,
NKT cells, and CD8aß T cells, has significant role in
mediating immune responses by stimulating innate
and adaptive immune (Kopp et al., 2009). Some study
found several polymorphisms in MICB gene (Raulet,
2003;
Steinle et al., 2001). MICB gene contains a
microsatellite polymorphism named C1_2_A in intron
1
comprising 16 alleles (Kopp et al., 2009).
The pathogenesis of DHF has been considered to the
massive immune activation of T cells and NK