Proteomic Characterization of Helicobacter pylori CagA Antigen Recognized by Child Serum Antibodies and Its Epitope Mapping by Peptide Array

Akada, Junko; Okuda, Masumi; Hiramoto, Narumi; Kitagawa, Takao; Zhang, Xiulian; Kamei, Satoshi; Ito, Akane; Nakamura, Masaji; Uchida, Tomohisa; Hiwatani, Tomoko; Fukuda, Yoshihiro; Nakazawa, Takahiro; Kuramitsu, Yasuhiro; Nakamura, Kazuyuki

doi:10.1371/journal.pone.0104611

Cited by 18 publications

(15 citation statements)

References 44 publications

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“…In the early 2000s, 80%–100% of H. pylori strains possessed the cagA gene in East Asia ( 18 19 ) and 94% were cagA -positive in H. pylori DNA extracts from 33 Korean children ( 20 ). In Japan, the CagA was the most reactive antigen recognized by all the H. pylori positive sera even from children under the age of 3 year ( 21 ). Therefore, the regional CagA antigens for serodiagnosis of H. pylori would be important, which could affect the rate of seropositivity ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Correlations between the CagA Antigen and Serum Levels of Anti-Helicobacter pyloriIgG and IgA in Children

et al. 2016

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We tested correlations between anti-Helicobacter pylori IgG and IgA levels and the urease test, anti-CagA protein antibody, degree of gastritis, and age. In total, 509 children (0–15 years) were enrolled. Subjects were stratified as 0–4 years (n = 132), 5–9 years (n = 274), and 10–15 years (n = 103) and subjected to the urease test, histopathology, ELISA, and western blot using whole-cell lysates of H. pylori strain 51. The positivity rate in the urease test (P = 0.003), the degree of chronic gastritis (P = 0.021), and H. pylori infiltration (P < 0.001) increased with age. The median titer for anti-H. pylori IgG was 732.5 IU/mL at 0–4 years, 689.0 IU/mL at 5–9 years, and 966.0 IU/mL at 10–15 years (P < 0.001); the median titer for anti-H. pylori IgA was 61.0 IU/mL at 0–4 years, 63.5 IU/mL at 5–9 years, and 75.0 IU/mL at 10–15 years (P < 0.001). The CagA-positivity rate was 26.5% at 0–4 years, 36.5% at 5–9 years, and 46.6% at 10–15 years for IgG (P = 0.036), and 11.3% at 0–4 years, 18.6% at 5–9 years, and 23.3% at 10–15 years for IgA (P < 0.001). Anti-H. pylori IgG and IgA titers increased with the urease test grade, chronic gastritis degree, active gastritis, and H. pylori infiltration. Presence of CagA-positivity is well correlated with a high urease test grade and high anti-H. pylori IgG/IgA levels.

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Section: Discussionmentioning

confidence: 99%

Correlations between the CagA Antigen and Serum Levels of Anti-Helicobacter pyloriIgG and IgA in Children

et al. 2016

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“…A related finding is that CagA is the most reactive antigen recognized by H . pylori -positive sera from children [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Microevolution of Virulence-Related Genes in Helicobacter pylori Familial Infection

et al. 2015

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Helicobacter pylori, a bacterial pathogen that can infect human stomach causing gastritis, ulcers and cancer, is known to have a high degree of genome/epigenome diversity as the result of mutation and recombination. The bacteria often infect in childhood and persist for the life of the host. One of the reasons of the rapid evolution of H. pylori is that it changes its genome drastically for adaptation to a new host. To investigate microevolution and adaptation of the H. pylori genome, we undertook whole genome sequencing of the same or very similar sequence type in multi-locus sequence typing (MLST) with seven genes in members of the same family consisting of parents and children in Japan. Detection of nucleotide substitutions revealed likely transmission pathways involving children. Nonsynonymous (amino acid changing) mutations were found in virulence-related genes (cag genes, vacA, hcpDX, tnfα, ggt, htrA and the collagenase gene), outer membrane protein (OMP) genes and other cell surface-related protein genes, signal transduction genes and restriction-modification genes. We reconstructed various pathways by which H. pylori can adapt to a new human host, and our results raised the possibility that the mutational changes in virulence-related genes have a role in adaptation to a child host. Changes in restriction-modification genes might remodel the methylome and transcriptome to help adaptation. This study has provided insights into H. pylori transmission and virulence and has implications for basic research as well as clinical practice.

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“…In 22 H. pylori -infected Japanese children aged 2–13 years, serum IgG distinguished reactive spots identified as CagA, CagA fragments, FlaA, Omp21/AlpB, and VacA on 2D immunoblots (8). The presence of CagA bands on 1D immunoblots correlated with the high titer of anti- H. pylori IgG antibody in children aged 0–15 years (9).…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pyloriAntigens Inducing Early Immune Response in Infants

et al. 2017

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To identify the Helicobacter pylori antigens operating during early infection in sera from infected infants using proteomics and immunoblot analysis. Two-dimensional (2D) large and small gel electrophoresis was performed using H. pylori strain 51. We performed 2D immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibody immunoblotting using small gels on sera collected at the Gyeongsang National University Hospital from 4–11-month-old infants confirmed with H. pylori infection by pre-embedding immunoelectron microscopy. Immunoblot spots appearing to represent early infection markers in infant sera were compared to those of the large 2D gel for H. pylori strain 51. Corresponding spots were analyzed by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS). The peptide fingerprints obtained were searched in the National Center for Biotechnology Information (NCBI) database. Eight infant patients were confirmed with H. pylori infection based on urease tests, histopathologic examinations, and pre-embedding immunoelectron microscopy. One infant showed a 2D IgM immunoblot pattern that seemed to represent early infection. Immunoblot spots were compared with those from whole-cell extracts of H. pylori strain 51 and 18 spots were excised, digested in gel, and analyzed by MALDI-TOF-MS. Of the 10 peptide fingerprints obtained, the H. pylori proteins flagellin A (FlaA), urease β subunit (UreB), pyruvate ferredoxin oxidoreductase (POR), and translation elongation factor Ts (EF-Ts) were identified and appeared to be active during the early infection periods. These results might aid identification of serological markers for the serodiagnosis of early H. pylori infection in infants.

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Proteomic Characterization of Helicobacter pylori CagA Antigen Recognized by Child Serum Antibodies and Its Epitope Mapping by Peptide Array

Cited by 18 publications

References 44 publications

Correlations between the CagA Antigen and Serum Levels of Anti-Helicobacter pyloriIgG and IgA in Children

Correlations between the CagA Antigen and Serum Levels of Anti-Helicobacter pyloriIgG and IgA in Children

Microevolution of Virulence-Related Genes in Helicobacter pylori Familial Infection

Helicobacter pyloriAntigens Inducing Early Immune Response in Infants

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