Anti-CagA Reactivity in Helicobacter pylori-Negative Subjects (A Comparison of Three Different Methods)

Emerging evidence suggests that infection byCagA-positive Helicobacter pylori strains is related tothe development of more serious gastroduodenal diseases,thus conferring to the determination of anti-CagA antibodies a relevant clinical significance inserological screenings. The detection of anti-CagApositivity in sera negative for anti-H. pyloriantibodies raises the question of whether thisapparently nonsense result is merely due to a falsepositive reaction. To address this issue, we comparedthree different methods for the detection of anti-CagAantibodies. In all, 272 selected sera from patients with precisely defined H. pylori status(positive or negative concordance of five tests, ie,histology by Giemsa in both antrum and corpus, rapidurease test, culture, [¹³C]urea breath test,IgG ELISA) were tested for anti-CagA reactivity by threedifferent techniques (western immunoblotting, ELISA, andrecombinant immunoblotting assay). In order to assessthe sensibility and specificity of each tests, we considered as true anti-CagApositive sera those with two out of three positiveresults. Sera from 70% of H. pylori-positive patientsand 10% from H. pylori-negative patients turned out to be true positives foranti-CagA antibodies. The three methods showed similarexcellent results, in terms of both sensitivity andspecificity, always over 93%. It is confirmed that aproportion of patients with a negative conventionalserology against H. pylori possess anti-CagA antibodiesin their sera. In this paper we demonstrate that it canhappen even in patients without any biological signs of actual H. pylori infection. The possibilitythat this can be due to a false positive laboratoryresult is very likely ruled out by the accuracy of thethree methods used. The clinical management of these patients needs further study on largerseries.