Responses of Endoscopy Patients in Ladakh, India, to Helicobacter pylori Whole-Cell and CagA Antigens

Abstract

Although Helicobacter pylori is a cosmopolitan colonizer of the human stomach, the responses among persons in remote populations from whom H. pylori was cultured have not been studied. We report on studies of 189 persons in the Ladakh region of India in whom serum immunoglobulin G responses to H. pylori whole-cell and CagA antigens were measured. H. pylori was isolated from 68 of these patients. An H. pylori whole-cell antigen derived from Ladakhi strains outperformed a similar antigen from U.S. strains, as determined by antigenspecific enzyme-linked immunosorbent assays. In total, 95% of the population was seropositive, including individuals responding only to the CagA antigen. Correlation with culture results showed that these were true positives and, therefore, that the H. pylori whole-cell serology was falsely negative in some cases. In addition to establishing a collection of H. pylori isolates from a remote area in the world, we show that use of H. pylori whole-cell and CagA serology together increases the sensitivity for the detection of colonization.Although humans in all parts of the world may be colonized with Helicobacter pylori (2, 11), most detailed studies correlating serology with bacterial culture have been conducted in industrialized countries or in urban centers in developing countries (5, 23). In part, this pattern stems from the relative difficulty of acquiring proper specimens from indigenous peoples in remote areas, where much of the infrastructure that permits clinical investigation and subsequent biomedical research is lacking (4).Ladakh, India, is a remote trans-Himalayan region that is sparsely populated, owing to its high elevation (Ն3,500 m) and lack of rainfall. Its population of about 220,000 consists of individuals of Tibetan-Buddhist ethnicity (about 70%) and of Muslims originating in the Baltistan area of Pakistan and other areas of India (about 30%). The majority of the Muslim subjects (Argons) are the descendants of Kashmiri Muslim fathers and Ladakhi Buddhist mothers. Anecdotally, residents of Leh, the capitol of Ladakh, have a high incidence of upper gastrointestinal (GI) tract complaints, and before the advent of antacids and histamine receptor-blocking agents, they were believed to have had a high incidence of peptic ulcers and upper GI tract bleeding. Given that most individuals in such an environment would be expected to carry H. pylori (11), we conducted field studies of H. pylori carriage and serology in Ladakh.In an initial serological survey, performed during the summer of 1995, approximately 380 randomly selected individuals were screened for H. pylori antibodies by using a serological field test kit (Quidel, Inc., San Diego, Calif.). Included were residents of small rural communities and of Leh, including Tibetan orphans. The results of this survey were that about 95% of Ladakhis were H. pylori seropositive whether or not they had any potentially relevant symptoms referable to the upper GI tract (S. Wall, N. Shah, and R. P. Novick, unpublished data).On the basis of ...

Enzyme-Linked Immunosorbent Assay forHelicobacter pyloriNeeds Adjustment for the Population Investigated

“…Other studies indicated that although antigenic variations do occur, they might not represent a major problem in serology (6,7). In a very recent study from India, however, the same group reported findings similar to ours, i.e., that local strains gave a higher sensitivity in a sonicate whole-cell ELISA (13). Our study thus confirms the observation of that study and expands it by showing that local strains will also result in a higher specificity.…”

“…Whether antigenic differences are important enough to influence diagnostic performance of serological assays has been debated (3,6,7,13). Early studies from Thailand indicated that assays based on local strains performed better than strains of other origin or commercial assays (3).…”

Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China

“…Individuals who were negative for both antibodies (WCÀ, CagAÀ) were classified as H. pylori seronegative, whereas individuals who were seropositive for either WC or CagA antibodies were classified as H. pylori seropositive. This classification system was selected because culture-based studies have shown that individuals who are negative for H. pylori WC antibodies but positive for CagA antibodies are true positives (Romero-Gallo et al, 2002). Seropositive individuals were further classified as carrying CagA-negative strains (WC þ , CagAÀ) or CagA-positive strains (WC þ or WCÀ, CagA þ ) (Romero-Gallo et al, 2002).…”

Transient and PersistentHelicobacter pyloriColonization in Native American Children

“…This ELISA has a sensitivity of 94.4% and a specificity of 92.5% (47) and also has been validated in multiple diverse populations (23,43,68). H. pylori culture-positive persons may be seropositive in the CagA assay in the absence of response to the WC antigen (54).…”