Evaluation of the Effects of Strain-Specific Antigen Variation on the Accuracy of Serologic Diagnosis of Helicobacter pylori Infection

Abstract

It has been suggested that enzyme immunoassay (EIA) kits validated in one region may yield variable diagnostic performance results in different regions, possibly due to strain-specific differences in antibody responses in different populations. We tested 13 C-urea breath test-characterized serum samples from 109 U.S. patients and 288 Japanese patients using enzyme immunoassay with different preparations of high-molecularweight cell-associated (HM-CAP) antigens that are conserved across Helicobacter pylori strains. Replicate antigens were prepared from five H. pylori clinical isolates. Eight antigen preparations were evaluated: two of U.S. origin and six of Japanese origin. The accuracies achieved with the eight antigen preparations ranged from 94.4 to 96.3% with the U.S. samples. With the Japanese samples the accuracies achieved ranged from 92.3 to 97.2%. Use of a pool of HM-CAP antigens prepared from isolates from Japan resulted in a higher median enzyme immunoassay value and slightly fewer samples with indeterminate results compared to the results obtained by use of the U.S. standard HM-CAP antigen for H. pylori-positive patients (accuracies, 97.2 and 92.3%, respectively), suggesting that variations in performance between both antigen source and patient population might be reduced by using antigens pooled from several strains.

Epidemiology of Helicobacter pylori infection

“…Marchildon et al. [26] evaluated the effects of strain‐specific antigen variation on the accuracy of serologic diagnosis of H. pylori in different populations. The authors tested serum samples from 109 US patients and 288 Japanese patients using EIA with different preparations of high‐molecular‐weight cell‐associated (HM‐CAP) antigens of H. pylori strains.…”

Fragmented CagA Protein is Highly Immunoreactive in Japanese Patients

“…A serum‐based EIA test of JHM‐CAP prepared by exactly the same procedure as that used to prepare HM‐CAP EIA has been developed. When this EIA kit was used in Japanese patients, the sensitivity and specificity were 97.4 and 96.4%, respectively, and the number of intermediate cases decreased dramatically [14]. We have also reported the accuracy of JHM‐CAP EIA and HM‐CAP EIA in Japanese children [16].…”

“…Four clinical isolate strains from four Japanese patients with different diseases were used for culture. The strain numbers and the characteristics of the patients were described as follows: strain 159A from patients with gastric ulcer; strain 193C from patients with gastric cancer; strain 198C from patients with gastric ulcer; and strain 225C from patients with functional dyspepsia [14]. All strains were cultured on 10‐cm‐diameter blood agar plates (Trypticase Soy Agar II with 5% sheep blood: Becton Dickinson and Company, Tokyo, Japan) at 37 °C in a microaerobic atmosphere (5% O 2 , 10% CO 2 , and 85% N 2 ) and 100% humidity for 48–72 hours.…”

“…HM‐CAP EIA was prepared from HM‐CAP purified from US clinical isolates [13]. A serum‐based EIA test using Japanese strain–derived high‐molecular‐weight proteins (JHM‐CAP) prepared by exactly the completely same procedure as for HM‐CAP has been developed [14]. The diagnostic performances of JHM‐CAP EIA (Scimedx Corp.) and HM‐CAP EIA in adult populations were reported using urea breath test (UBT) as the gold standard.…”

“…The diagnostic performances of JHM‐CAP EIA (Scimedx Corp.) and HM‐CAP EIA in adult populations were reported using urea breath test (UBT) as the gold standard. For serum samples of Japanese populations, the performance of the JHM‐CAP EIA was better than that of the HM‐CAP EIA [14,15], although there was no difference between them on the accuracy in the serum samples from U.S. population. In addition, we have previously reported that in asymptomatic Japanese children under 10 years of age, the performance of JHM‐CAP immunoassay was statistically better than that of HM‐CAP EIA and found that the higher sensitivity of JHM‐CAP was because of the presence of an immunoreactive 100‐kDa protein, which was absent in HM‐CAP[16].…”