TY - JOUR
T1 - Identification of anti-Helicobacter pylori antibody signatures in gastric intestinal metaplasia
AU - Song, Lusheng
AU - Song, Minkyo
AU - Rabkin, Charles S.
AU - Chung, Yunro
AU - Williams, Stacy
AU - Torres, Javier
AU - Corvalan, Alejandro H.
AU - Gonzalez, Robinson
AU - Bellolio, Enrique
AU - Shome, Mahasish
AU - LaBaer, Joshua
AU - Qiu, Ji
AU - Camargo, M. Constanza
N1 - Funding Information:
The authors thank the production team and NAPPA core facility at the ASU Biodesign Center for Personalized Diagnostic for providing support on H. pylori NAPPA production. We would also like to thank Peter Khan, Al Burner and Peter Wicktor at Engineering Arts, LLC for NAPPA printing. The following reagent was obtained through BEI Resources, NIAID and NIH as part of the Human Microbiome Project: H. pylori Gateway®Clone Set, Recombinant in Escherichia coli , Plates 1–20 (BEI Resources NR-19477 through NR-19496), catalog No. NR-19275. We acknowledge the original contributor “Pathogen Functional Genomics Resource Center at the J. Craig Venter Institute” and BEI resources for providing the H. pylori clones set. We also appreciate the provision of cagA clones by Laurent Terradot at Institut de Biologie et Chimie des Protéines, France.
Publisher Copyright:
© 2022, Japanese Society of Gastroenterology.
PY - 2023/2
Y1 - 2023/2
N2 - Background: Chronic Helicobacter pylori infection may induce gastric intestinal metaplasia (IM). We compared anti-H. pylori antibody profiles between IM cases and non-atrophic gastritis (NAG) controls. Methods: We evaluated humoral responses to 1528 H. pylori proteins among a discovery set of 50 IM and 50 NAG using H. pylori protein arrays. Antibodies with ≥ 20% sensitivity at 90% specificity for either group were selected and further validated in an independent set of 100 IM and 100 NAG using odds ratios (OR). A validated multi-signature was evaluated using the area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI). Results: Sixty-two immunoglobulin (Ig) G and 11 IgA antibodies were detected in > 10%. Among them, 22 IgG and 6 IgA antibodies were different between IM and NAG in the discovery set. Validated antibodies included 11 IgG (anti-HP1177/Omp27/HopQ [OR = 8.1, p < 0.001], anti-HP0547/CagA [4.6, p < 0.001], anti-HP0596/Tipα [4.0, p = 0.002], anti-HP0103/TlpB [3.8, p = 0.001], anti-HP1125/PalA/Omp18 [3.1, p = 0.001], anti-HP0153/RecA [0.48, p = 0.03], anti-HP0385 [0.41, p = 0.006], anti-HP0243/TlpB [0.39, p = 0.016], anti-HP0371/FabE [0.37, p = 0.017], anti-HP0900/HypB/AccB [0.35, p = 0.048], and anti-HP0709 [0.30, p = 0.003]), and 2 IgA (anti-HP1125/PalA/Omp18 [2.7, p = 0.03] and anti-HP0596/Tipα [2.5, p = 0.027]). A model including all 11 IgG antibodies (AUC = 0.81) had better discriminated IM and NAG compared with an anti-CagA only (AUC = 0.77) model (NRI = 0.44; p = 0.001). Conclusions: Our study represents the most comprehensive assessment of anti-H. pylori antibody profiles in IM. The target antigens for these novel antibodies may act together with CagA in the progression to IM. Along with other biomarkers, specific H. pylori antibodies may identify IM patients, who would benefit from surveillance.
AB - Background: Chronic Helicobacter pylori infection may induce gastric intestinal metaplasia (IM). We compared anti-H. pylori antibody profiles between IM cases and non-atrophic gastritis (NAG) controls. Methods: We evaluated humoral responses to 1528 H. pylori proteins among a discovery set of 50 IM and 50 NAG using H. pylori protein arrays. Antibodies with ≥ 20% sensitivity at 90% specificity for either group were selected and further validated in an independent set of 100 IM and 100 NAG using odds ratios (OR). A validated multi-signature was evaluated using the area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI). Results: Sixty-two immunoglobulin (Ig) G and 11 IgA antibodies were detected in > 10%. Among them, 22 IgG and 6 IgA antibodies were different between IM and NAG in the discovery set. Validated antibodies included 11 IgG (anti-HP1177/Omp27/HopQ [OR = 8.1, p < 0.001], anti-HP0547/CagA [4.6, p < 0.001], anti-HP0596/Tipα [4.0, p = 0.002], anti-HP0103/TlpB [3.8, p = 0.001], anti-HP1125/PalA/Omp18 [3.1, p = 0.001], anti-HP0153/RecA [0.48, p = 0.03], anti-HP0385 [0.41, p = 0.006], anti-HP0243/TlpB [0.39, p = 0.016], anti-HP0371/FabE [0.37, p = 0.017], anti-HP0900/HypB/AccB [0.35, p = 0.048], and anti-HP0709 [0.30, p = 0.003]), and 2 IgA (anti-HP1125/PalA/Omp18 [2.7, p = 0.03] and anti-HP0596/Tipα [2.5, p = 0.027]). A model including all 11 IgG antibodies (AUC = 0.81) had better discriminated IM and NAG compared with an anti-CagA only (AUC = 0.77) model (NRI = 0.44; p = 0.001). Conclusions: Our study represents the most comprehensive assessment of anti-H. pylori antibody profiles in IM. The target antigens for these novel antibodies may act together with CagA in the progression to IM. Along with other biomarkers, specific H. pylori antibodies may identify IM patients, who would benefit from surveillance.
KW - H. pylori
KW - Intestinal metaplasia
KW - NAPPA
KW - Premalignant lesions
KW - Serology
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U2 - 10.1007/s00535-022-01933-0
DO - 10.1007/s00535-022-01933-0
M3 - Article
C2 - 36301365
AN - SCOPUS:85140595949
SN - 0944-1174
VL - 58
SP - 112
EP - 124
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
IS - 2
ER -