Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
2000-03-09
2002-09-17
Fredman, Jeffrey (Department: 1634)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S091200, C435S005000, C536S023100
Reexamination Certificate
active
06451533
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a
Helicobacter pylori
gene whose expression is associated with mucosa-associated lymphoid tissue lymphoma of the stomach (MALToma), and the use of the DNA composing the gene and the protein encoded by the DNA for detecting predisposition to MALToma.
BACKGROUND OF THE INVENTION
Helicobacter pylori,
a spiral gram-negative bacterium, was first isolated in 1982 from the gastric mucosa of a patient with gastritis and peptic ulceration (Marshall B. J. and Warren J. R.,
Lancet,
1984, 1:1311-1315). Since then, there is strong evidence showing that
H. pylori
is the causative agent of chronic active gastritis and has an important role in duodenal ulcerogenesis (Blaser M. J.,
Sci. Am.,
1996, 274:104-107). It has been documented that the relapse rate of both duodenal and gastric ulcers decreases dramatically after eradication of
H. pylori,
and cure of this chronic relapsing disease (Graham D. Y. et. al.,
Ann. Intern. Med.,
1992, 116:705-708; Hentschel E. et. al.,
N. Engl. J. Med.,
1993, 328:308-312). The infection by
H. pylori
has also been shown to be associated with adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach (Nomura A. et. al.,
N. Engl. J. Med.,
1991, 325:1132-1136; Parsonnet J. et. al.,
N. Engl. J. Med.,
1991, 325:1127-1131; Bayerdorffer E. et. al.,
Lancet,
1995, 345:1591-1594). Although the prevalence of this infection and MALToma is high, only a few infected subjects develop clinically significant diseases. Most patients remain asymptomatic (Blaser M. J.,
Sci. Am.,
1996, 274:104-107).
To eradicate the infection in all patients is not feasible in terms of cost, compliance, and possible drug resistance. In addition, variation in host genetic background, environmental factors, and virulence of the bacterial strains may contribute to different clinical outcomes (Blaser M. J.,
Sci. Am.,
1996, 274:104-107). Therefore, it would be useful to find a candidate marker to differentiate the strains that are more harmful to the host. Hence, the inventors of the present application have tried to find a specific antigen of
H. pylori
associated with gastric MALToma using an immunoscreening strategy.
An objective of the invention is to identify specific antigen(s) from
H. pylori
strains associated with gastric MALToma, which seems to depend on the stimulation of
H. pylori.
Another objective of the invention is to use the gastric MALToma associated protein, FldA, and its encoding DNA, including its mutant forms, to identify patients with higher risk of developing gastric MALToma.
Still another objective of the invention is to use antibodies against FldA or its truncated protein as a serological marker to screen for patients infected with
H. pylori
that are in high risk of developing gastric MALToma.
SUMMARY OF THE INVENTION
The present invention provides methods for screening patients infected with
H. pylori
that are in high risk of developing gastric MALToma by the following:
1) using antibodies against the surface antigens, FldA, of
H. pylori;
2) using molecular biology techniques, such as DNA sequencing, DNA probe, gene chip, RT-PCR, or Southern hybridization, to detect the expression of fldA; and
3) using the mutation of the fldA gene of
H. pylori
to detect gastric MALToma at early stage.
In one of the preferred embodiments, the present invention discloses a method of using a FldA protein for screening patients infected with
Helicobacter pylori
that are in a high risk of developing mucosa-associated lymphoid tissue lymphoma of the stomach comprising contacting antibody-containing samples from patients with a 19-kilodalton FldA protein from
Helicobacter pylor.
Preferably, said 19-kilodalton FldA protein is encoded by a putative flavodoxin gene (fldA) from
Helicobacter pylori
having a guanidine insertion at a position of 481.
Preferably, an ELISA method or a Western blot method is used to detect the presence of said 19-kilodalton FldA protein in said antibody-containing samples from patients.
Preferably, said antibody-containing samples from patients contain antibodies which are polyclonal or monoclonal antibodies.
In another preferred embodiments, the present invention discloses a method of using a putative flavodoxin gene (fldA) from
Helicobacter pylori
for screening patients infected with
Helicobacter pylori
that are in a high risk of developing mucosa-associated lymphoid tissue lymphoma of the stomach comprising using a molecular biology technique to detect the expression of fldA gene of
Helicobacter pylori
from patients so that a guanidine insertion at a position of 481 of said fldA gene can be determined.
Preferably, said molecular biology technique is DNA sequencing, DNA probe, gene chip, RT-PCR, or Southern hybridization.
More preferably, said fldA gene has a sequence listing defined in FIG.
4
A.
REFERENCES:
patent: 5403924 (1995-04-01), Cover et al.
Cover et al. Gastroenterology. 1999. vol. 117, No. 1, pp. 257-260.*
Liu et al. Gastroenterology. 2000. vol. 118, No. 5, pp. 988-989.*
Chang et al., “Isolation of aHelicobacter PyloriProtein, FldA, Associated with Mucosa-Associated lymphoid Tissue Lymphoma Of the Stomach”, Gastroenterology 117:82-88, 1999.
Chang Chih-Shen
Chang Kai-Chih
Chen Li-Tzong
Lin Jaw-Tow
Wang Jin-Town
Einsmann Juliet
Fish & Richardson P.C.
Fredman Jeffrey
National Science Council
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