In order to investigate the differential contribution
of Hp infection to LG in an inflammatory condition like CD, the gastric tissue
inflammatory subpopulation profile was investigated, by immunohistochemistry,
and compared between the 4 groups of patients. Past studies focused mainly on
the surface epithelial infiltrate as well as on the superficial pit gastric
epithelium invasion by lymphocytes, and to a lesser extent on the infiltrate in
the LP and in the gastric glands.
The main finding of the
present study was the highest prevalence LG in pediatric CD+Hp- followed by CD-Hp+.
Forty five percent of CD
patients are estimated to have LG like in our study [8
]. However, LG appears
to be similarly frequent in Hp positive children with and without CD [13
Previous studies demonstrated that LG was found to be more common in Hp
positive children without CD than in Hp negative children without CD. The IELs
were almost exclusively T cells [14
]. There are still controversial results on
the contribution of CD and Hp infection to LG. Moreover, the association
between these pathologies to LG is not well established [13
gastritis was reported in 36–45% of children with CD [6
], and disappears
after a gluten free diet. Hp infection is less frequently found in patients
with LG [13%] than with the usual chronic antral gastritis [65–90%] [13
]. CD is
considered to be a population at greatest risk for LG compared to Hp affected
Our study confirmed the
published results of an increased number of IELs in both CD and Hp infected
patients. The most prominent LG was found in CD patients without Hp infection.
Surprisingly, CD patients with associated Hp infection showed a lower rate of
LG. This evidence might be explained by the well known limited roll of
bacterial infection in cytotoxicity. Hp convergent the immune response towards
Th2 response and suppress the Th1 immune response.
have published several sets of data concerning the composition of the
lymphocytic infiltrates in the different diseases [16
]. Drut et al found
that LG in pediatric CD patients contains a peculiar CD3, CD7 and CD8
intraepithelial lymphocyte population, that is not associated with the presence
of CD4, CD20, CD56 and CD57 IELs [21
]. In Hp gastritis there is an increased
number of mononuclear cells in the gastric LP, including B and T lymphocytes, plasma cells, macrophages and mast
cells. Lymphoid aggregates are particularly characteristic of Hp infection
]. It has been shown that Hp stimulates B lymphocytes and causes an increase
in their numbers predominantly in the LP [23
]. Although immunity against Hp
infection appears not to be dependent on B cells, the role of T cells still
remains to be clarified [24
]. It appears however that the B cell proliferation
might be driven by activated lymphocytes (CD4+ cells) that might recall and
activate mononuclear phagocytes.
Bedoya et al. demonstrated
that the cellular response includes an innate nonspecific response represented
mainly by polymorphonuclear cells and macrophages, as well as a T cell response
with abundant positive staining with anti-CD8 antibodies, was observed
indicative of a predominance of suppressor/cytotoxic T lymphocytes both in the
LP and in the epithelium [22
Similarly we also showed
the presence of CD3+ IELs in both diseases (CD; Hp infection). Despite a
potential additive effect between these two pathological processes, it is
impossible to differentiate between them, based only on the number of the CD3+
IELs in the antral mucosa. CD3 staining is a pan T lymphocyte marker and does
not differentiate between CD4 helper and CD8 suppressor/cytotoxic cells,
therefore we aimed to characterize the T cell subsets immunophenotype (CD4+,
In our study the CD8+
IELs were significantly higher in CD patients (20/100 epithelial cells),
compared to controls (1/100 epithelial cells) or Hp infected patients without
CD (2/100 epithelial cells). We assume that in undiagnosed patients with
histological features compatible with LG, higher counts of CD8+ IELs may imply
that the diagnosis is CD rather than Hp gastritis. Our findings support the
published data that CD8+/CD4− IELs are involved significantly in the
pathogenesis of CD [25
In our study, the low expression of CD57 in
the lymphoid cells, both in the epithelium, in the LP as well as in the mucosal
glands indicate that NK cells may play a negligible role in these two pathologies.
We also tried to differentiate between
these two causative agents of LG by looking at the proliferation marker, Ki67.
Although both conditions were associated with a prominent adaptive immune
activity, no increase in the proliferation index of the surface epithelium was
demonstrated in these pathologies.
Dendritic cells (CNA42+) which serve as
professional antigen presenting cells did not show an increased expression in
both pathologies. This may indicate that the process of antigen presentation
occurred in the lymph nodes. This notion is supported by the absence of CD4 (T
helper) cells in the immune cell infiltrates found in the affected tissues.
Thus, in the infected area we observed mainly the effector CD8 lymphocytes.
In addition to all the
above, we confirmed the published results that the highest number of lymphoid
follicles was observed in a similar proportion of children with or without CD,
who were Hp positive independent of the presence of LG.
infiltrate in the LP and in the mucosal glands does not contribute to the
differentiation between these diseases.
In summary, our study
aimed to explore the contribution of CD and Hp infection to LG and to
characterize the different immunoprofiles of the gastric inflammatory cells
involved in these diseases. We were looking for an applicable histological tool
that might differentiate between cases of CD and Hp infection with overlapping
clinical and histological features.
We suggest that in very
young patients infected by Hp and suspicion for having atypical CD (negative
serology with increased IELs with normal villous architecture-Marsh I
classification) with a debatable diagnosis of CD versus Hp infection, the
number of CD8+ IELs in the antrum might hint toward the diagnosis of CD rather
than Hp infection, and the number of lymphoid follicles directs toward the
diagnosis of Hp infection. Thus, it is important to include immunohistochemical
analysis of CD8 lymphocytes in the antrum in undefined cases of CD.