Helicobacter pylori vacA genotype is a predominant determinant of immune response to Helicobacter pylori CagA

To evaluate the frequency of ( ) CagA antibodies in infected subjects and to identify potential histopathological and bacterial factors related to CagA-immune response. Systematic data to isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospec...

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Published inWorld journal of gastroenterology : WJG Vol. 23; no. 26; pp. 4712 - 4723
Main Authors Link, Alexander, Langner, Cosima, Schirrmeister, Wiebke, Habendorf, Wiebke, Weigt, Jochen, Venerito, Marino, Tammer, Ina, Schlüter, Dirk, Schlaermann, Philipp, Meyer, Thomas F, Wex, Thomas, Malfertheiner, Peter
Format Journal Article
LanguageEnglish
Published United States Baishideng Publishing Group Inc 14.07.2017
Subjects
Adult
Aged
Antigens, Bacterial - immunology
Bacterial Proteins - immunology
Basic Study
Female
Helicobacter Infections - immunology
Helicobacter pylori - genetics
Helicobacter pylori - immunology
Humans
Male
Middle Aged
Prospective Studies
VacA
Seropositivity
Immune response
Helicobacter pylori
Virulence factors
CagA
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Summary:To evaluate the frequency of ( ) CagA antibodies in infected subjects and to identify potential histopathological and bacterial factors related to CagA-immune response. Systematic data to isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti- , anti-CagA) was correlated with isolates ( , EPIYA, genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected strains were assessed for CagA protein expression and IL-8 induction in co-cultivation model with AGS cells. Thirty point three percent of microbiologically confirmed infected patients were seropositive for CagA. Majority of isolates were gene positive (93.9%) with following polymorphisms: 42.4% , 23.2% and 34.3% . Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and mRNA expression. and polymorphisms were the major determinants for positive ( s1m1) or negative ( s2m2) anti-CagA serological immune response, which also correlated with the inflammatory potential in AGS cells. co-cultivation of representative strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting as major co-determinant of the immune response. Serological immune response to + strain in infected patients is strongly associated with polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.
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Correspondence to: Alexander Link, MD, PhD, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. alexander.link@med.ovgu.de
Author contributions: Link A and Langner C contributed equally to this work; Link A, Wex T and Malfertheiner P designed the research; Link A, Langner C, Schirrmeister W, Habendorf W, Tammer I, Schlaermann P and Wex T performed the research; Link A, Schirrmeister W and Schlaermann P contributed new reagents/analytic tools; Link A, Langner C, Schlaermann P, Wex T and Malfertheiner P analyzed the data; Link A, Langner C and Malfertheiner P wrote the paper; all authors revised and approved the final version of the paper.
Supported by the BMBF No. BMBF-0315905D in the frame of ERA-NET PathoGenoMics to Malfertheiner P.
Telephone: +49-391-6713100 Fax: +49-391-6713105
ISSN:1007-9327
2219-2840
2219-2840
DOI:10.3748/wjg.v23.i26.4712