Seroreactivity against Helicobacter pylori VacA, 50 kDa, and 30 kDa along with alarm features may improve the diagnostic approach to uninvestigated dyspepsia – a pilot study

  • Nebojša Manojlović Military Medical Academy, Clinic for Gastroenterology and Hepatology, Belgrade, Serbia
  • Ivana Tufegdžić University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
  • Elizabeta Ristanović University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
  • Dubravko Bokonjic
Keywords: antigens, biomarkers, duodenal neoplasms, duodenal ulcers, gastroscopy, helicobacter pylori, stomach neoplasms, stomach ulcer

Abstract


Background/Aim. Alarm features (AF) are of limited utility in predicting endoscopic findings, and the majority of patients with uninvestigated dyspepsia will have no organic pathology identified at upper gastrointestinal endoscopy. In our previous study, we highlighted seroreactivity against Helicobacter pylori (HP) antigens VacA, 50 kDa, and 30 kDa as biomarkers for gastric cancer, peptic ulcers, and functional dyspepsia. We designed and conducted this pilot study in order to compare the diagnostic utility of seroreactivity against HP VacA, 50 kDa, and 30 kDa with AF and investigate the possibility and adequacy of its synchronous application. Method. A careful history and physical examination with special attention to AF, esophagogastroduodenoscopy with biopsy, abdominal ultrasound or computer tomography, complete blood count (CBC) and blood biochemistry, a Western Blot IgG against HP antigens VacA, 50 kDa, and 30 kDa, were performed in 123 patients with dyspepsia: 31 with gastric cancer, 31 with duodenal ulcer, 31 with gastric ulcer, and 30 with gastritis and functional dyspepsia. AF vs various combinations of seroreactivity against HP VacA, 50 kDa, and 30 kDa in patients with functional dyspepsia and others were analyzed in this study. Synchronous and alternative seroreactivity against VacA, 50 kDa, and 30 kDa, along with/without AF in patients with functional dyspepsia and other groups of patients were also analyzed. Results. VacA and 50 kDa seropositivity or AF had excellent case-findings clinical utility index for investigating dyspepsia. The absence of AF and seroreactivity against VacA either with: 50 kDa or 30 kDa seropositivity or 50 kDa and 30 kDa seropositivity had an excellent screening clinical utility index for investigating dyspepsia. Conclusion. Seroreactivity against HP antigens VacA, 50 kDa, and 30 kDa might improve our approach to patients in investigating dyspepsia if used along with AF.

References

Zagari RM, Fuccio L, Bazzoli F. Investigating dyspepsia. BMJ 2008; 337: a1400.

Black CJ, Houghton LA, Ford AC. Insights into the evaluation and management of dyspepsia: recent developments and new guidelines. Therap Adv Gastroenterol 2018; 11: 1756284818805597.

Talley NJ, Vakil NB, Moayyedi P. American gastroenterological association technical review on the evaluation of dyspepsia. Gastroenterology 2005; 129(5): 1756‒80.

Vakil N, Moayyedi P, Fennerty MB, Talley NJ. Limited value of alarm features in the diagnosis of upper gastrointestinal malig-nancy: systematic review and meta-analysis. Gastroenterology 2006; 131(2): 390‒401; quiz 659‒60.

Manojlović N, Tufegdžić I, Ristanović E, Bokonjić D. Serum IgG antibodies against Helicobacter pylori low molecular weight anti-gens 50kDa, 30kDa and Urease A 26 kDa, along with Vacuo-lating cytotoxin A are associated with the outcome of infec-tion. Vojnosanit Pregl 2020; 77(4): 405‒12.

Manojlović N, Tufegdzic I, Ristanović E, Bokonjić D. Simultaneous and alternative IgG seroreactivity against Helicobacter pylori an-tigens VacA, 30 kDa and 50 kDa is better biomarker approach for the outcome of infection than VacA and 50 kDa alone. Vojnosanit Pregl 2020; DOI: 10.2298/VSP200116071M.

Hassan TMM, Al-Najjar SI, Al-Zahrani IH, Alanazi FIB, Alo-tibi MG. Helicobacter pylori chronic gastritis updated Sydney grading in relation to endoscopic findings and H. pylori IgG antibody: diagnostic methods. J Microsc Ultrastruct 2016; 4(4): 167‒74.

Sipponen P, Maaroos HI. Chronic gastritis. Scand J Gastroenter-ol 2015; 50(6): 657‒67.

Mitchell AJ. Sensitivity x PPV is a recognized test called the clinical utility index (CUI+). Eur J Epidemiol 2011; 26(3): 251‒2; author reply 252.

Bossuyt PM, Reitsma JB, Linnet K, Moons KG. Beyond diagnostic accuracy: the clinical utility of diagnostic tests. Clin Chem 2012; 58(12): 1636-43.

Lee SW, Chang CS, Yeh HJ, Lien HC, Lee TY, Peng YC. The Diagnostic Value of Alarm Features for Identifying Types and Stages of Upper Gastrointestinal Malignancies. Gastroenterol-ogy Res 2017; 10(2): 120‒5.

Jung HK. Systematic Review With Meta-analysis: Prompt En-doscopy As the Initial Management Strategy for Uninvestigat-ed Dyspepsia in Asi (Aliment Pharmacol Ther 2015; 41:239–252). J Neurogastroenterol Motil 2015; 21(3): 443‒4.

Kapoor N, Bassi A, Sturgess R, Bodger K. Predictive value of alarm features in a rapid access upper gastrointestinal cancer service. Gut 2005; 54(1): 40–5.

Chen SL, Gwee KA, Lee JS, Miwa H, Suzuki H, Guo P, et al. Systematic review with meta-analysis: prompt endoscopy as the initial management strategy for uninvestigated dyspepsia in Asia. Aliment Pharmacol Ther 2015; 41(3): 239‒52.

Heikkinen M, Pikkarainen P, Takala J, Räsänen H, Julkunen R. Etiology of dyspepsia: four hundred unselected consecutive patients in general practice. Scand J Gastroenterol 1995; 30(6): 519‒23.

Abdeljawad K, Wehbeh A, Qayed E. Low Prevalence of Clinical-ly Significant Endoscopic Findings in Outpatients with Dys-pepsia. Gastroenterol Res Pract 2017; 2017: 3543681.

Odeghe EA, Adeniyi OF, Oyeleke GK, Keshinro SO. Use of alarm features in predicting significant endoscopic findings in Nige-rian patients with dyspepsia. Pan Afr Med J 2019; 34: 66.

Wallace MB, Durkalski VL, Vaughan J, Palesch YY, Libby ED, Jowell PS, et al. Age and alarm symptoms do not predict endo-scopic findings among patients with dyspepsia: a multicentre database study. Gut 2001; 49(1): 29‒34.

Bai Y, Li ZS, Zou DW, Wu RP, Yao YZ, Jin ZD, et al. Alarm features and age for predicting upper gastrointestinal malig-nancy in Chinese patients with dyspepsia with high back-ground prevalence of Helicobacter pylori infection and upper gastrointestinal malignancy: an endoscopic database review of 102,665 patients from 1996 to 2006. Gut 2010; 59(6): 722‒8.

Schmidt N, Peitz U, Lippert H, Malfertheiner P. Missing gastric cancer in dyspepsia. Aliment Pharmacol Ther 2005; 21(7): 813‒20.

Suzuki H, Oda I, Abe S, Sekiguchi M, Mori G, Nonaka S, et al. High rate of 5-year survival among patients with early gastric cancer undergoing curative endoscopic submucosal dissection. Gastric Cancer 2016; 19(1): 198‒205.

Katai H, Ishikawa T, Akazawa K, Isobe Y, Miyashiro I, Oda I, et al. Five-year survival analysis of surgically resected gastric can-cer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001-2007). Gastric Cancer 2018; 21(1): 144‒54.

Asplund J, Kauppila JH, Mattsson F, Lagergren J. Survival Trends in Gastric Adenocarcinoma: A Population-Based Study in Sweden. Ann Surg Oncol 2018; 25(9): 2693‒702.

Maconi G, Kurihara H, Panizzo V, Russo A, Cristaldi M, Marrelli D, et al. Gastric cancer in young patients with no alarm symp-toms: focus on delay in diagnosis, stage of neoplasm and sur-vival. Scand J Gastroenterol. 2003; 38(12): 1249‒55.

Kishikawa H, Kimura K, Takarabe S, Kaida S, Nishida J. Helico-bacter pylori Antibody Titer and Gastric Cancer Screening. Dis Markers 2015; 2015: 156719.

Manojlovic N, Babic D, Filipovic-Ljeshovic I, Pilcevic D. Anti Heli-cobacter pylori IgG and IgA response in patients with gastric cancer and chronic gastritis. Hepatogastroenterology 2008; 55(82‒83): 807‒13.

Manojlovic N, Nikolic L, Pilcevic D, Josifovski J, Babic D. Systemic humoral anti-Helicobacter pylori immune response in patients with gastric malignancies and benign gastroduodenal disease. Hepatogastroenterology 2004; 51(55): 282‒4.

Zagari RM, Rabitti S, Greenwood DC, Eusebi LH, Vestito A, Bazzoli F. Systematic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diag-nosis of atrophic gastritis. Aliment Pharmacol Ther 2017; 46(7): 657‒67.

Hammer J. Identification of Individuals with Functional Dys-pepsia With a Simple, Minimally Invasive Test: A Single Cen-ter Cohort Study of the Oral Capsaicin Test. Am J Gastroen-terol 2018; 113(4): 584‒92.

Chomvarin C, Ottiwet O, Hahnvajanawong C, Intapan PM, Wongwa-jana S. Seroreactivity to specific antigens of Helicobacter pylori infection is associated with an increased risk of the dyspeptic gastrointestinal diseases. Int J Infect Dis 2009; 13(5): 647‒54.

Schumann C, Triantafilou K, Rasche FM, Möricke A, Vogt K, Tri-antafilou M, et al. Serum antibody positivity for distinct Helico-bacter pylori antigens in benign and malignant gastroduodenal disease. Int J Med Microbiol 2006; 296(4‒5): 223‒8.

Karami N, Talebkhan Y, Saberi S, Esmaeili M, Oghalaie A, Ab-dirad A, et al. Seroreactivity to Helicobacter pylori antigens as a risk indicator of gastric cancer. Asian Pac J Cancer Prev 2013; 14(3): 1813‒7.

Chua TS, Fock KM, Chan YH, Dhamodaran S, Sim CS, Ng TM, et al. Seroreactivity to 19.5-kDa antigen in combination with absence of seroreactivity to 35-kDa antigen is associated with an increased risk of gastric adenocarcinoma. Helicobacter 2002; 7(4): 257‒64.

Janulaityte-Günther D, Kupcinskas L, Pavilonis A, Valuckas K, Wadström T, Andersen LP. Combined serum IgG response to Helicobacter pylori VacA and CagA predicts gastric cancer. FEMS Immunol Med Microbiol 2007; 50(2): 220‒5.

Aucher P, Petit ML, Mannant PR, Pezennec L, Babin P, Fauchere JL. Use of immunoblot assay to define serum antibody pat-terns associated with Helicobacter pylori infection and with H. pylori-related ulcers. J Clin Microbiol 1998; 36(4): 931‒6.

Lamarque D, Gilbert T, Roudot-Thoraval F, Deforges L, Chaumette MT, Delchier JC. Seroprevalence of eight Helicobacter pylori antigens among 182 patients with peptic ulcer, MALT gastric lymphoma or non-ulcer dyspepsia. Higher rate of seroreactivi-ty against CagA and 35-kDa antigens in patients with peptic ulcer originating from Europe and Africa. Eur J Gastroenterol Hepatol 1999; 11(7): 721‒6.

Filipec Kanizaj T, Katicić M, Presecki V, Gasparov S, Colić Cvrlje V, Kolarić B, et al. Serum antibodies positivity to 12 Helicobac-ter pylori virulence antigens in patients with benign or malig-nant gastroduodenal diseases-cross-sectional study. Croat Med J 2009; 50(2): 124‒32.

Published
2022/07/13
Section
Original Paper