Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer.
Helicobacter pylori has been associated with gastritis, peptic ulcer, and gastric adenocarcinoma. We report the nucleotide sequence and expression of an immunodominant antigen of H. pylori and the immune response to the antigen during disease. The antigen, named CagA (cytotoxin-associated gene A), is a hydrophilic, surface-exposed protein of 128 kDa produced by most clinical isolates. The size of the cagA gene and its protein varies in different strains by a mechanism that involves duplication of regions within the gene. Clinical isolates that do not produce the antigen do not have the gene and are unable to produce an active vacuolating cytotoxin. An ELISA to detect the immune response against a recombinant fragment of this protein detects 75.3% of patients with gastroduodenal diseases and 100% of patients with duodenal ulcer (P < 0.0005), suggesting that only bacteria harboring this protein are associated with disease.
Covacci
A
A
Immunobiological Research Institute Siena, Italy.
Censini
S
S
Bugnoli
M
M
Petracca
R
R
Burroni
D
D
Macchia
G
G
Massone
A
A
Papini
E
E
Xiang
Z
Z
Figura
N
N
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D001782:Blood Donors; D015139:Blotting, Southern; D002876:Chromosomes, Bacterial; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D004381:Duodenal Ulcer / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D015698:Genomic Library; D016480:Helicobacter pylori / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D012016:Reference Values; D015183:Restriction Mapping; D013276:Stomach Ulcer / Q000382:microbiology; D014774:Virulence / Q000235:genetics
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D009838:Oligodeoxyribonucleotides; C080866:cagA protein, Helicobacter pylori