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Clinical and Diagnostic Laboratory Immunology, July 1999, p. 633-638, Vol. 6, No. 4
1071-412X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Serum Antibody Responses to Helicobacter
pylori and the cagA Marker in Patients with
Mucosa-Associated Lymphoid Tissue Lymphoma
Anne
Taupin,1
Alessandra
Occhialini,1
Agnès
Ruskone-Fourmestraux,2
Jean-Charles
Delchier,3
Jean-Claude
Rambaud,4 and
Francis
Mégraud1,*
Laboratoire de Bactériologie,
Université de Bordeaux 2, 33076 Bordeaux
Cedex,1 Service de
Gastroentérologie, Hôtel-Dieu de Paris, 75181 Paris
Cedex 4,2 Service
d'Hépatogastroentérologie, Hôpital Henri Mondor,
94010 Créteil,3 and Service de
Gastroénterologie, Hôpital Lariboisière, 75475 Paris
cedex 10,4 France
Received 5 August 1998/Returned for modification 28 December
1998/Accepted 13 April 1999
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ABSTRACT |
The lymphoma of the mucosa-associated lymphoid tissue (MALT) of the
stomach has been linked to Helicobacter pylori infection, but the mechanisms involved in B-cell proliferation remain elusive. In
a search for putative H. pylori-specific monoclonal
immunoglobulin production, an H. pylori strain was isolated
from 10 patients with MALT lymphoma and used to detect the specific
serum antibody response to the homologous strain by immunoblotting.
Moreover, the antigenicity of the different strains was compared by
using each of the 10 sera. We found that the different strains induced highly variable patterns of systemic immunoglobulin G antibody response, although several bacterial antigens, such as the 60-kDa urease B, were often recognized by the different sera. The
cagA marker was detected in the strains by PCR with
specific primers and by dot blot analysis, and the CagA protein was
found in the sera of 4 of the 10 patients by immunoblotting. In
conclusion, MALT lymphoma patients, like other patients with H. pylori gastritis, exhibit a polymorphic systemic antibody
response, despite an apparently similar antigenic profile. The CagA
marker of pathogenicity is not associated with this disease.
| |
TEXT |
Since the discovery of
Helicobacter pylori and its pathogenic role in gastric and
duodenal ulceration, it has also been associated with gastric
adenocarcinomas. Recently, an association between the presence of
H. pylori and the development of mucosa-associated lymphoid
tissue (MALT) B-cell gastric lymphoma has been documented (12). H. pylori infection was found in 85 to 92%
of patients with this malignancy (17, 24). Carlson et al.
observed the progression of H. pylori gastritis with
polyclonal lymphoid hyperplasia to a MALT lymphoma with a monoclonal
lymphoid population (4). Moreover, among a series of six
patients with low-grade MALT lymphoma, five patients displayed complete
regression of their lymphomas upon eradication of H. pylori
by antibiotherapy. Therefore, MALT lymphoma appears in the stomach in
response to colonization by the bacterium and regresses after treatment
of H. pylori infection (1, 2, 4, 13-15, 19, 23,
24). Gastric MALT lymphoma has a low incidence of occurrence
(seven cases per 1 million people per year in the United States), but
it is the most common type of extranodal lymphoma (8). It
seems to occur more frequently in certain parts of Europe, such as
northeastern Italy (9).
The mechanisms by which this bacterial infection leads to the
development of MALT lymphoma have not yet been elucidated. MALT is not
found in normal gastric mucosa but is assumed to develop after
infection. It is possible that the pattern of evolution of low-grade
MALT lymphomas is dependent on a local immune response to a specific
antigen. In the case of gastric lymphomas, an abnormal immune response
to H. pylori in the gastric mucosa and gastric lymph nodes
may be associated with proliferation of neoplastic B cells. There are
few cases where the strains and the patients' sera are available.
Therefore, the immune response of the patient to his or her homologous
strain has not been previously studied.
The aim of this study was to analyze, by immunoblotting, the serum
antibody response to H. pylori strains from 10 patients with
MALT lymphoma, in order to define a typical pattern for this pathology.
In addition, because the cag pathogenicity island has been associated
with severe diseases due to H. pylori, the immune response
to the CagA marker was studied. Strains were also analyzed by PCR and
dot blot analysis to detect the presence of the cagA gene.
Patients.
Ten patients (four females and six males) bearing
B-lymphocytic low-grade gastric MALT lymphomas (stage IE or IIE) were
studied. For each patient, two gastric biopsy specimens were collected, one at the site of the lesion and one at a distance from it. Biopsies were transported to the laboratory by using Portagerm pylori medium (bioMérieux, Marcy l'Etoile, France) and processed as follows: they were ground in brucella broth and inoculated onto nonselective Wilkins-Chalgren medium and GC agar base supplemented with 5% human
blood. After 12 days of incubation at 37°C under microaerobic conditions, growing colonies were identified as H. pylori by
morphology and positive reactions for urease, catalase, and oxidase. At
the time of the sampling, blood was drawn, and serum was collected, aliquoted, and kept frozen at 
20°C until use. Eight of these patients have subsequently received an
omeprazole-clarithromycin-amoxicillin therapy which was successful, and
seven of them are still in remission.
ELISA and immunoblot analysis.
An enzyme-linked immunosorbent
assay (ELISA) for H. pylori was performed with the
experimental Pylori Check enzyme immunoassay kit (Hoffmann-La Roche,
Basel, Switzerland). Immunoblot analysis was performed with the
Helico-Blot 2.0 kit (Genelabs Diagnostics, Geneva, Switzerland). The
strain of H. pylori used in the Helico-Blot 2.0 was a
clinical isolate (ATCC 43256) from an ulcer. These two assays were
conducted following the manufacturer's recommendations.
An in-house immunoblot was also used. The antigens used were made from
H. pylori strains isolated from the patients' biopsies. Colonies from two semiconfluent plates were harvested, washed twice in
phosphate-buffered saline (PBS), resuspended in 0.3 ml of PBS, and
sonicated for 3 min with a Vibra cell apparatus (Sonics and Materials
Inc., Danbury, Conn.). The sonicates were centrifuged to discard
debris, and the supernatants were retained. After determination of the
protein concentration with a protein assay (Bio-Rad, Ivry sur Seine,
France), the sonicates were adjusted to 1 mg of protein per ml,
aliquoted, and frozen at 20°C until use. Immediately before use,
sonicates were diluted in sample loading buffer (0.5 M Tris-HCl [pH
6.8], 0.5% bromophenol blue, 8% glycerol, 4% sodium dodecyl sulfate
[SDS], 4% 2-mercaptoethanol) and the mixture was heated at 95°C
for 5 min. After cooling, 5 µg of H. pylori proteins was
loaded on each lane of SDS-10% polyacrylamide gels, under reducing
conditions, and proteins were separated by electrophoresis.
Molecular weight standards (Bethesda Research Laboratories, Bethesda,
Md.), which included proteins ranging from 14.3 to 200 kDa, were
treated similarly. Proteins were then transferred to nitrocellulose
sheets (Bio-Rad, Richmond, Calif.) by using a semidry electroblotter
(Biolyon, Dardilly, France) at 12 V for 10 min, followed immediately by
24 V for 1 h. Nonspecific binding sites on the nitrocellulose
membrane were then saturated with Tris-buffered saline containing 0.5%
Tween 20 and 3% fat-free milk for 1 h at room temperature. After
3 washes with Tris-buffered saline-Tween buffer, the nitrocellulose
tracks were incubated with the different sera diluted 1/50 and 1/100 in
washing buffer, under gentle agitation, for 2 h at room
temperature. Membranes were washed three times and incubated with
horseradish peroxidase-labelled goat anti-human immunoglobulin G (IgG)
conjugate (Nordic, Tilburg, The Netherlands) for 1 h diluted 1/500
in washing buffer. After another three washes, immunoblots were
developed by using 4-chloro-naphthol (Sigma, L'Isle-d'Abeau-Chêne, France) as a substrate.
The immunoblot patterns were analyzed with Gelcompar software (Applied
Maths, Kortrijk, Belgium): molecular sizes of the stained
bands were
determined by comparing them with protein markers ranging
from 14.3 to
200 kDa, and the intensity of the staining was calculated
following
densitometric integration of the nitrocellulose tracks.
Faint bands
(less than 3% staining for any given track) were not
considered for
data
interpretation.
The sera were tested by using a Pylori Check enzyme immunoassay and
immunoblot (Helico-Blot 2.0), and found to contain IgG
antibodies
against
H. pylori in both assays (Table
1). The intensity
of the ELISA was
usually positively correlated with the number
and the intensity of the
bands seen in the immunoblot (Fig.
1).
However, some discrepancies were noted between these two assays
(Fig.
1, lane 2). Major differences appeared when the band patterns
in the
immunoblot were compared for these 10 patients. Several
bands, such as
those corresponding to the 19- to 20-, 26.5-, 35-,
and 116-kDa
antigens, were recognized by very few patients.
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FIG. 1.
Anti-H. pylori serum antibody response
assessed by the Helico-Blot 2.0 immunoblot in nine patients with MALT
lymphoma. Patterns displayed are for patients 1, 5, 6, 3, 8, 4, 7, 2, and 10 (lanes 1 to 9, respectively) and for positive and negative
controls (lanes 10 and 11, respectively).
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The results obtained with the Helico-Blot 2.0 assay prompted us to
analyze the immunoblot patterns with the homologous strain,
i.e., the
strain infecting each patient. As an example, Fig.
2 displays the immunoblot patterns for
the strains isolated from
patients 1, 5, and 6, tested with the serum
from the corresponding
patient (lanes 1 and 2, 3 and 4, and 7 and 8, respectively). The
antibody response against the antigens of the
homologous strain
(1/50 and 1/100 dilutions in odd- and even-numbered
lanes, respectively)
was generally greater than that against the
antigens of the strain
used in the Helico-Blot 2.0, in terms of number
of bands. The
same set of bands were recognized by serum antibodies,
including
proteins migrating at 20, 26 to 28, 30, 37, 40 to 42, 50, 54,
60, 67, 70, and 89 kDa. However, not all the sera reacted with
all of
these antigens. The sera with a mild response against the
antigens used
in the Helico-Blot 2.0 stained very few bands when
tested against the
homologous strain. A more precise comparison
of this response did not
single out any specific antigen(s) present
in the strain isolated from
patients with lymphomas and absent
in the reference strain.
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FIG. 2.
Anti-H. pylori serum antibody response
assessed by immunoblot by using homologous and heterologous strains.
Lysates from the strains isolated from patients 1, 5, and 6 (A, B, and
C, respectively) were used as antigens to detect anti-H.
pylori antibodies in the serum from seven patients with MALT
lymphoma. The sera tested were from patients 1 (lanes 1 and 2), 5 (lanes 3 and 4), 9 (lanes 5 and 6), 6 (lanes 7 and 8), 3 (lanes 9 and
10), 8 (lanes 11 and 12), 4 (lanes 13 and 14), and 7 (lanes 15 and 16).
Positive and negative control sera (lanes 17 and 18 and lanes 19 and
20, respectively) were included. Two dilutions were tested: 1/50
(odd-numbered lanes) and 1/100 (even-numbered lanes).
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The protein profile of the strains was performed by SDS-polyacrylamide
gel electrophoresis (PAGE). The cells were washed twice
in 1 ml of PBS
solution and centrifuged at 6,000 ×
g for 5 min.
The
pellets were resuspended in 200 µl of PBS and boiled at 100°C
for 5 min. Proteins (15 µl) were separated on an SDS-polyacrylamide
gel
(29% acrylamide, 1%
N,
N'-methylenebisacrylamide) through a
stacking
gel (5%) for 1 h at 100 V and through a resolving gel
(10%) for
4 h at 135 V (
20). Polypeptides separated by SDS-PAGE
were stained with Coomassie brilliant blue for 1 h and destained
in a methanol-acetyl acid solution (45% [vol/vol] of each reagent)
overnight. The profiles of the different strains were indeed similar
(Fig.
3).
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FIG. 3.
SDS-PAGE of the proteins of the 10 strains of H. pylori. The proteins were from strains isolated from patients 5, 9, 6, 3, 8, 4, 7, 10, 2, and 1 (lanes 1 to 10, respectively) and from
strain 26695 (lane 11). M, molecular mass standard proteins (Mid-Range
proteins; Promega). The numbers on the left indicate the molecular
weights (in thousands) of the proteins.
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Each of the 10 sera was tested against the nine heterologous strains
isolated from the nine other patients. Representative
patterns are
displayed in Fig.
2 for strains isolated from three
patients, against
which seven serum samples from seven patients
were tested (1/50
dilution, odd-numbered lanes, and 1/100 dilution,
even-numbered lanes).
The immune response against
H. pylori also
appeared very
different from one patient to another, as already
suggested by the
Helico-Blot 2.0 assay. Several antigens elicited
a strong antibody
response with the heterologous sera, such as
the strain from patient 1 with serum from patient 4 or 8 (Fig.
2B, lanes 11 to 14), with a major
band at 60 kDa, as judged from
the staining with a heterologous strain,
although they were mildly
recognizable with the homologous strain (Fig.
2A, lane 2). This
same antigen was strongly recognized with serum from
patient 7,
incubated with its homologous strain (not shown) as well as
with
the heterologous strains from patients 1 and 5 (Fig.
2A and B,
lanes 15 and 16, respectively). When the antibody response to
the
homologous strain was weak, in terms of number of bands, it
reacted
similarly toward the heterologous strains. This was the
case for serum
from patient 5 with strains from patients 1, 5,
and 6 (Fig.
2A, B, and
C, lanes 3 and 4, respectively). Globally,
the patterns were very
different for any given strain and the
10 sera tested with
it.
Analysis of the cagA gene of H. pylori.
The
presence of the cagA gene was analyzed by PCR and dot blot
analysis. The DNA of H. pylori cultures was extracted by the standard phenol-chloroform procedure. Briefly, the cells were harvested
in 2 ml of brucella broth from two 48-h-old culture plates, and they
were centrifuged at 4,000 × g for 15 min. The pellets
of bacteria were resuspended in 2 ml of a buffer containing 10 mM
Tris-HCl (pH 8.0) and 1 mM EDTA. They were then treated successively
with SDS (1%) and proteinase K (0.1 g/liter). Proteins were eliminated
by solvent extraction (twice with phenol and once with chloroform). DNA
was precipitated with 95% ethanol at 20°C in the presence of 0.3 M
sodium (pH 4.8). The DNA pellet was washed with 75% ethanol, dried,
and resuspended in water.
Two pairs of primers previously described (
21) were used for
detection of two internal regions of the
cagA gene (GenBank
accession no.
U60176). First, 5'-GAT AAC AGG CAA CGT TTT CAG
GGA-3'
(positions 19119 to 19142) and 5'-CCG AAC GGA TCA AAA ATT
CAT GG-3'
(19512 to 19490), named cagA1 and cagA2, were used to
amplify a 394-bp
section of the
cagA region (
21). Second, 5'-ATG
GGG AGT CAT GAT GGC ATA GAA CC-3' (19872 to 19897) and 5'-GGT
GGC TGT
CTT TAA TTT GCC TAA T-3' (20588 to 20564), named cagA3
and cagA4, were
used to amplify a 717-bp fragment (
21). PCR
conditions were
optimized with the reference strain CCUG 17864
by using a 480 thermal
cycler (Perkin-Elmer Corp., Norwalk, Conn.).
PCR amplification was
performed in a final volume of 50 µl containing
1 ng of
H. pylori DNA with 67 mM Tris-HCl (pH 8.8), 16 mM
(NH
4)
2SO
4,
0.01% Tween 20, 1.5 mM
MgCl
2, 50 pmol of each primer, 1 U of Gold
Start Red
Taq DNA polymerase (Eurogentec Bel. A., Seraing, Belgium),
and a 0.2 mM concentration of deoxynucleoside triphosphate mixture
(Eurobio). The amplicons were analyzed on a 1% agarose
gel.
The amplification cycles consisted of an initial denaturation of the
target DNA at 94°C for 5 min and then denaturation at
94°C for 1 min, primer annealing at 62°C for 1 min, and extension
at 72°C for
1 min (2 min for the second set of primers), repeated
in 35 consecutive
cycles. The final cycle included an extension
step at 72°C for 5 min
to ensure full extension of the product.
Furthermore, two other primers
were used for amplification of
the complete
cagA gene (cagA5
and cagA6). The primers, chosen
by comparing the sequences of the
cagA gene in strains J99, 26695,
and CCUG 17874 (GenBank
accession no.
U60176), are as follows:
cagA5, 5'-TAG GTA TAG TAA GGA
GAA ACA ATG ACT AAC G-3' (positions
18942 to 18972), and cagA6, 5'-CCT
TAA TCC TTT AAG ATT TTT GGA
AAC CAC C-3' (22416 to 22386). All the
primers were synthesized
by Eurogentec. The last PCR was performed with
a 9600 thermal
cycler (Perkin-Elmer). The amplification cycles
consisted of an
initial denaturation at 94°C for 1 min, primer
annealing at 60°C
for 2 min, and extension at 72°C for 5 min; the
final cycle included
an extension step at 72°C for 7 min. All PCR
products were run
on 1% agarose gels and stained with ethidium
bromide.
The amplified products cagA5 and cagA6 of the reference strain obtained
by PCR were used as probes in the hybridization experiments.
The
amplicons were electrophoresed on a 1% agarose gel, cut out
of the
gel, and purified with a QIAEX II gel extraction kit (Qiagen,
Courtaboeuf, France). DNA probes were labelled with an enhanced
chemiluminescence kit according to the conditions (hybridization
at
42°C and washing steps at 55°C) specified by the supplier
(Amersham,
Little Chalfont, Buckinghamshire, United Kingdom). For the
dot
blot analysis, 300 ng of undigested denatured total DNA was
transferred
to a blot membrane by means of a Bio-Rad slot blot
apparatus.
Four of the 10 strains (from patients 1, 3, 4, and 6) had a positive
result, with primer pairs cagA1-cagA2 and cagA3-cagA4
detecting the
cagA gene (Fig.
4). In the
same strains, the complete
cagA gene sequence was also
detected with a pair of primers from
the extremity of the
cagA gene, allowing the amplification of
3,474 bp. For six
strains, the
cagA gene was absent and false-negative
results
were ruled out by amplification of the 16S rRNA gene of
H. pylori. Dot blot analysis was then performed on all strains
with
the cagA5-cagA6 probe, and it confirmed the PCR results.
Immunoblot
analysis with the 10 sera against the strain isolated
from PCR-positive
patient 6 (Fig.
2C) showed the presence of a
120- to 140-kDa band,
corresponding in size to the CagA protein,
in the four patients for
whom the
cagA gene was present.
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FIG. 4.
Detection of the cagA gene by PCR in strains
obtained from MALT lymphoma patients. (A) PCR amplifications with
primers cagA1 and cagA2 (394 bp). (B) PCR amplifications with primers
cagA3 and cagA4 (717 bp). The amplicons are for strains isolated from
patients 5, 9, 6, 3, 8, 4, 7, 10, 2, and 1 (lanes 1 to 10, respectively); reference strain 26695 (lane 11); and the negative
control (lane 12). M,  X174 DNA/Hae III markers (Eurobio).
The numbers on the left indicate the molecular sizes (in base pairs) of
DNA.
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Normal gastric mucosa does not contain lymphoid tissue, but lymphocytes
are recruited upon colonization of the stomach by
the bacterium. In
vitro experiments have shown that
H. pylori stimulates the
proliferation of B-lymphoma cells in cultures of
gastric biopsies
(
11,
12). This cellular proliferation is
abolished when the
T lymphocytes associated with the MALT are
eliminated. Therefore, the
occurrence of B-lymphoma cells is dependent
on the presence of T
cells.
The malignant proliferation is monoclonal, as shown by the study of the
molecular rearrangement of the immunoglobulin heavy-chain
genes
(
3,
16). It is not known whether the bacterium triggers
or
selects B lymphocytes specific for its own antigen; i.e., it
has not
been shown thus far whether the B-lymphoma cells are capable
of
producing an
H. pylori-specific monoclonal antibody. Another
unanswered question deals with the nature of the stimulating antigen,
if it
exists.
A comparative study by immunoblot of the serum antibody response
against
H. pylori in 10 patients with MALT lymphoma was
undertaken.
All the patients studied produced anti-
H. pylori
antibodies, as
shown by ELISA and Western blot analysis. However, the
immunoblot
pattern was very different among the patients, suggesting
great
variability in individuals' capacities to react to
H. pylori antigens.
In view of these differences, the antibody
response against the
homologous strains isolated from the gastric
biopsies was studied.
As with the commercial reagent, there was
considerable variation
among the individual patients' responses toward
their own strains.
No band that was recognized by all the sera tested
and was not
known to be present in other
H. pylori-associated diseases was
detected.
A positive conclusion of this study is the variability in the systemic
immune response observed which does not differentiate
MALT lymphoma
patients from other infected persons. The cause
of this variability is
believed to be linked to the immune response
rather than to the
antigenic composition of the strain. However,
patients 1 and 5 displayed some specificity for their own strains.
This fact could be
explained by a broadening, over time, of the
specificity of the immune
response, but sera collected at different
times in the natural course
of the infection were not available
to confirm this hypothesis.
Alternatively, it is possible that,
in fact, only a few clones of
H. pylori with minor protein variation,
even if undetectable
by SDS-PAGE, do exist. Indeed, the results
of the randomly amplified
polymorphic DNA analysis performed on
the strains showed different
profiles (data not
shown).
Moreover, a similar conclusion can be drawn from the comparative study
of the response against the nine heterologous strains
isolated from the
nine other patients. The results strongly suggested
that no typical
pattern was associated with this particular disease
state. For most
patients and strains, no abnormally strong reaction
against any antigen
could be seen. This indicates that no monoclonal
antibody against
H. pylori was circulating in the serum of these
patients, at
least at a titer high enough to be detected. Alternatively,
this
putative monoclonal antibody may be confined to the gastric
tissue and
not released into the bloodstream. Another possibility
is that it does
not belong to the IgG isotype. We tried to detect
an IgA response to
H. pylori, but antibody titers were always
very low or
undetectable (data not shown). However, the systemic
antibody response
might not reflect very well the local gastric
antibody response. To
exclude a local monoclonal antibody response,
immunoglobulin from the
gastric juice should have been tested.
Unfortunately, such samples were
not
available.
Another interesting antigen of
H. pylori is the CagA
protein. It is a high-molecular-mass protein, approximately 120 to 140
kDa, which is present in 80 to 100% of the strains responsible
for
duodenal ulcers and in 70% of the strains responsible for
gastric
ulcers, but only in 50 to 60% of the strains responsible
for nonulcer
dyspepsia (
6) (percentages are based on strains
isolated
from Western countries). This immunodominant protein
is encoded by the
cagA gene and is a marker for the presence of
the cag
pathogenicity island (
5). In the present study, 4 out
of the
10 sera tested reacted against a protein of this size and
possessed the
cagA gene, as assessed by different
tests.
The association of
cagA+ strains with MALT
lymphoma is controversial. The first studies did not show an
association: de Jong
et al. (
7) and Witherell et al.
(
22) reported 12 and 32 cases,
respectively. Later Eck et
al. (
10) claimed that 95% of MALT
lymphomas occurred with
cagA+ strains. Their series included 46 high-grade and 22 low-grade
MALT lymphomas. Peng et al. (
18)
subsequently confirmed that
cagA+ strains are
more frequent in high-grade than in low-grade MALT
lymphomas.
This study demonstrates that a large variety of
H. pylori
strains can be considered responsible for the induction of MALT
lymphoma, as judged from the heterogeneity of their antigenic
properties, and that the
cagA marker does not seem to be
associated
with the disease. However, the local response as well as
other
markers remains to be
studied.
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FOOTNOTES |
*
Corresponding author. Mailing address: Laboratoire de
Bactériologie, Université de Bordeaux 2, 33076 Bordeaux
Cedex, France. Phone: (33) 5-56-79-59-10. Fax: (33) 5-56-79-60-18. E-mail: francis.megraud{at}chu-aquitaine.fr.
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REFERENCES |
| 1.
|
Bayerdörffer, E.,
A. Neubauer,
B. Rudolph,
C. Thiede,
N. Lehn,
S. Eidt, and M. Stolte.
1995.
Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection.
Lancet
345:1591-1594[Medline].
|
| 2.
|
Boot, H.,
D. de Jong,
P. van Heerde, and B. Taal.
1995.
Role of Helicobacter pylori eradication in high-grade MALT lymphoma.
Lancet
346:448-449[Medline].
|
| 3.
|
Calvert, R.,
P. E. Randerson,
P. Evans,
L. Cawkwell,
F. Lewis,
M. F. Dixon, and G. J. Morgan.
1995.
Genetic abnormalities during transition from Helicobacter pylori associated gastritis to low-grade MALToma.
Lancet
345:2626-2627.
|
| 4.
|
Carlson, S. J.,
H. Yokoo, and A. Vanagunas.
1996.
Progression of gastritis to monoclonal B-cell lymphoma with resolution and recurrence following eradication of Helicobacter pylori.
JAMA
275:937-939[Abstract/Free Full Text].
|
| 5.
|
Censini, S.,
C. Lange,
Z. Xiang,
J. E. Crabtree,
P. Ghiara,
M. Borodovski,
R. Rappuoli, and A. Covacci.
1996.
Cag, a pathogenicity island of Helicobacter pylori, encodes type 1-specific and disease-associated virulence factors.
Proc. Natl. Acad. Sci. USA
93:14648-14653[Abstract/Free Full Text].
|
| 6.
|
Covacci, A.,
S. Censini,
M. Bugnoli,
R. Petracca,
D. Burroni,
G. Macchia,
A. Massone,
E. Papini,
Z. Xiang,
N. Figura, and R. Rappuoli.
1993.
Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer.
Proc. Natl. Acad. Sci. USA
90:5791-5795[Abstract/Free Full Text].
|
| 7.
|
de Jong, D.,
R. W. van der Hulst,
G. Pals,
W. C. van Dijk,
A. van der Ende,
G. N. Tytgat,
B. G. Taal, and H. Boot.
1996.
Gastric non-Hodgkin lymphomas of mucosa-associated lymphoid tissue are not associated with more aggressive Helicobacter pylori strains as identified by CagA.
Am. J. Clin. Pathol.
106:670-675[Medline].
|
| 8.
|
Delchier, J. C.
1997.
Lymphomes gastriques. Aspects cliniques, p. 151-160.
In
F. Mégraud, and H. Lamouliatte (ed.), Helicobacter pylori, clinique, traitement, vol. 2. Elsevier Option Bio, Paris, France.
|
| 9.
|
Doglioni, C.,
A. C. Wotherspoon,
A. Moschini,
M. de Boni, and P. G. Isaacson.
1992.
High incidence of primary gastric lymphoma in northeastern Italy.
Lancet
339:834-835[Medline].
|
| 10.
|
Eck, M.,
B. Schmausser,
R. Haas,
A. Greiner,
S. Czub, and H. K. Muller-Hermelink.
1997.
MALT-type lymphoma of the stomach is associated with Helicobacter pylori strains expressing the CagA protein.
Gastroenterology
112:1482-1486[Medline].
|
| 11.
|
Hussell, T.,
P. G. Isaacson,
J. E. Crabtree, and J. Spencer.
1993.
The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori.
Lancet
342:571-574[Medline].
|
| 12.
|
Isaacson, P. G., and J. Spencer.
1995.
The biology of low grade MALT lymphoma.
J. Clin. Pathol.
48:395-397[Free Full Text].
|
| 13.
|
Levine, M. S.,
N. Elmas,
E. E. Furth,
S. E. Rubesin, and M. I. Goldwein.
1996.
Helicobacter pylori and gastric MALT lymphoma.
Am. J. Roentgenol.
166:85-86[Free Full Text].
|
| 14.
|
Montalban, C.,
D. Boixeda, and C. Bellas.
1996.
Helicobacter pylori eradication in gastric mucosa-associated lymphoid tissue lymphomas.
Ann. Intern. Med.
124:275.
|
| 15.
|
Montalban, C.,
A. Manzanal,
D. Boixeda,
C. Redondo, and C. Bellas.
1995.
Treatment of low-grade gastric MALT lymphoma with Helicobacter pylori eradication.
Lancet
345:798-799[Medline].
|
| 16.
|
Okazaki, K.,
M. Morita, and Y. Yamamoto.
1994.
Gene rearrangements, Helicobacter pylori, and gastric MALT lymphoma.
Lancet
343:1636[Medline].
|
| 17.
|
Parsonnet, J.,
S. Hansen,
L. Rodriguez,
A. B. Geld,
R. A. Warnke,
E. Jellum,
N. Orentreich,
J. H. Vogelman, and G. D. Friedman.
1994.
Helicobacter pylori infection and gastric lymphoma.
N. Engl. J. Med.
330:1267-1270[Abstract/Free Full Text].
|
| 18.
|
Peng, H.,
R. Ranaldi,
T. C. Diss,
P. G. Isaacson,
I. Bearzi, and L. Pan.
1998.
High frequency of CagA+ Helicobacter pylori infection in high-grade gastric MALT B-cell lymphomas.
J. Pathol.
185:409-412[Medline].
|
| 19.
|
Roggero, E.,
E. Zucca,
G. Pinotti,
A. Pascarella,
C. Capella,
A. Savio,
E. Pedrinis,
A. Paterlini,
A. Venco, and F. Cavalli.
1995.
Eradication of Helicobacter pylori infection in primary low-grade gastric lymphoma of mucosa-associated lymphoid tissue.
Ann. Intern. Med.
122:767-769[Abstract/Free Full Text].
|
| 20.
|
Sambrook, J.,
E. F. Fritsch, and T. Maniatis.
1989.
Molecular cloning: a laboratory manual, 2nd ed.
Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.
|
| 21.
|
Tummuru, M. K.,
T. L. Cover, and M. J. Blaser.
1993.
Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production.
Infect. Immun.
61:1799-1809[Abstract/Free Full Text].
|
| 22.
|
Witherell, H. L.,
S. Hansen,
E. Jellum,
N. Orentreich,
J. H. Vogelman, and J. Parsonnet.
1997.
Risk for gastric lymphoma in persons with CagA+ and CagA Helicobacter pylori infection.
J. Infect. Dis.
176:1641-1644[Medline].
|
| 23.
|
Wotherspoon, A. C.,
C. Doglioni,
M. de Boni,
J. Spencer, and P. G. Isaacson.
1994.
Antibiotic treatment for low-grade gastric MALT lymphoma.
Lancet
343:1503[Medline].
|
| 24.
|
Wotherspoon, A. C.,
C. Doglioni,
T. C. Diss,
L. Pan,
A. Moschini,
M. de Boni, and P. G. Isaacson.
1993.
Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori.
Lancet
342:575-577[Medline].
|
Clinical and Diagnostic Laboratory Immunology, July 1999, p. 633-638, Vol. 6, No. 4
1071-412X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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