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Intestinal dendritic cells are continually exposed to ingested microorganisms and high concentrations of endogenous bacterial flora. These cells can be activated by infectious agents and other stimuli to induce T-cell responses and to produce chemokines which recruit other cells to the local environment. Bacterial probiotics are of increasing use against intestinal disorders such as inflammatory bowel disease. They act as nonpathogenic stimuli within the gut to regain immunologic quiescence. This study was designed to determine the ability of a bacterial probiotic cocktail VSL#3 to alter cell surface antigen expression and cytokine production in bone marrow-derived dendritic cell-enriched populations. Cell surface phenotype was monitored by monoclonal fluorescent antibody staining, and cytokine levels were quantitated by enzyme-linked immunosorbent assay. High-dose probiotic upregulated the expression of C80, CD86, CD40, and major histocompatibility complex class II I-Ad. Neither B7-DC or B7RP-1 was augmented after low-dose probiotic orLactobacillus caseitreatment, but B7RP-1 showed increased expression on dendritic cells stimulated with the gram-negative bacteriumEscherichia coli. Functional studies showed that probiotic did not enhance the ability of dendritic cells to induce allogeneic T-cell proliferation, as was observed forE. coli. Substantial enhancement of interleukin-10 release was observed in dendritic cell-enriched culture supernatants after 3 days of probiotic stimulation. These results demonstrate that probiotics possess the ability to modulate dendritic cell surface phenotype and cytokine release in granulocyte-macrophage colony-stimulating factor-stimulated bone marrow-derived dendritic cells. Regulation of dendritic cell cytokines by probiotics may contribute to the benefit of these molecules in treatment of intestinal diseases.

Background Active gastritis, gastric mucosal atrophy and intestinal metaplasia are lesions associated with Helicobacter pylori infection. Atrophy and intestinal metaplasia are only seen in adults. Objectives We describe pediatric patients with atrophy and metaplasia, and compare the inflammatory response in these patients to controls. Methods As part of a multicenter study of pediatric H. pylori infection, gastric biopsy specimens obtained during diagnostic upper endoscopy of 19 H. pylori-infected children and 45 uninfected controls were reviewed and graded by using the updated Sydney system. The inflammatory response was characterized using immunohistochemistry for T lymphocytes, B lymphocytes, and macrophages, and TUNEL assay for apoptosis. Results Histology of H. pylori-infected and control biopsy specimens showed active gastritis in 32% and 2% respectively (P = 0.002). Mild intestinal metaplasia was found in 4 H. pylori-infected children, in two of whom it appeared to be accompanied by atrophy. Specimens from patients with H. pylori infection contained increased numbers of B lymphocytes in lymphoid nodules, and apoptosis in the superficial epithelium and inflammatory cells. T lymphocytes and macrophages appeared in similar numbers in specimens from controls and infected patients. Conclusions We describe intestinal metaplasia associated with H. pylori infection in children. Since atrophy usually precedes intestinal metaplasia in adults, we suggest that atrophy exists in children. High numbers of B lymphocytes and apoptosis in the surface epithelium are seen in patients with H. pylori infection and may be related to the development of atrophy and intestinal metaplasia.

To test the hypothesis that a Th2 response toHelicobacter pyloriis necessary for protection and to address the possibility that humoral and Th2 cellular responses may compensate for each other, we generated mice deficient in both interleukin-4 (IL-4) and antibodies. The immunized double-knockout mice were protected fromH. pylorichallenge, as were the parental strains and wild-type C57BL/6 mice. Neutralization of IL-4 in B-cell-deficient mice did not prevent protection. Immunized IL-5-deficient mice were also protected. Thus, IL-4 and IL-5 are not essential for protection.

Helicobacterpyloriinfection of the gastric mucosa is a significant cause of morbidity and mortality because of its etiologic role in symptomatic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Infection occurs in young children; therefore, a prophylactic vaccine would have to be administered within the first year of life, a period thought to be immunologically privileged. We investigated vaccine formulations administered by different routes to confer protective anti-H.pyloriimmunity in neonatal mice. Neonatal mice immunized with a single dose of vaccine in complete Freund's adjuvant (CFA) generated antigen-specific gamma interferon-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in numbers similar to those in immunized adult mice, while vaccine administered to neonates in incomplete Freund's adjuvant (IFA) induced such cells in reduced numbers compared to those in adult mice. Both IFA and CFA, however, provided partial protection from a challenge with infectiousH. pyloriwhen the vaccine was administered subcutaneously. Neonatal immunized mice also had reduced bacterial loads when immunized intraperitoneally with CFA. In all cases, protection was equivalent to that achieved when adult counterparts were immunized. These studies suggest that an efficacious vaccine might be successfully administered to very young children to prevent perinatal infection ofH.pylori.

Despite federally legislated safety regulations, caustic ingestions remain a significant problem in the pediatric population. The current standard of care for caustic ingestion includes upper gastrointestinal endoscopy in most cases. Hair relaxers are a common caustic ingestion at our institution, yet few data have been published describing the clinical or endoscopic outcome. We explored the relative frequency of hair relaxer ingestion, the incidence of associated upper gastrointestinal injury, and the adverse clinical sequelae resulting from these ingestions.Consecutive caustic ingestions admitted to our institution between January 1990 and January 2001 were identified. The data were collected through retrospective physician chart review, were analyzed, and were pooled with the existing literature to evaluate for the presence of esophageal injury.96 charts were reviewed, 29 (30%) of which were hair relaxer ingestions that underwent esophagogastroduodenoscopy; these ingestions served as our study cohort. The median age of the cohort was 14.0 months and patients were evenly divided in gender. The most common symptoms at presentation were drooling and emesis. At endoscopy, lip and oropharyngeal mucosa were most commonly affected. While six patients (20.7%) had Grade I esophageal mucosal injury and five patients (17.2%) had Grade I gastric mucosal injury, none had greater than Grade I mucosal damage. No adverse clinical events were identified. When our data were combined with all previously published cohort data, the findings were similar and no adverse clinical outcomes were reported.Hair relaxer is the most common childhood caustic ingestion presenting to our large metropolitan tertiary care center. Symptoms are common at presentation. However, despite the high pH of these products, no clinically significant esophageal or gastric mucosal injuries and no long-term sequelae were identified.

Gastric inflammation is a significant contributor to the disease process associated with Helicobacter pylori infection. It appears that both bacterial genes and differential host responses make interrelated contributions to gastritis and disease outcome after H. pylori infection. While the cag pathogenicity island (PAI) continues to be a focus for much of this investigation on the bacterial side, other bacterial genes/proteins are certainly important as well. On the host cell side, significant progress is being made defining the eucaryotic signaling cascades induced after host cells interact with H. pylori. The role of host cell cytokines, gastric acid, and mast cells is also being actively studied. Prospects for control of H. pylori associated disease continue to include vaccination. The mechanism(s) for vaccine-mediated control of H. pylori infection and disease remain ill-defined but recent evidence from animal models suggests that the inflammatory response may be involved. Manipulating the host response to H. pylori infection in humans to take advantage of the possible beneficial effects of inflammation, while minimizing its detrimental effects is a significant challenge for the future.

Patients infected withHelicobacter pylorimount an immune response which fails to clear the infection and may contribute to disease. Mice can be protected by immunization. To further characterize theH. pylori-mouse model, stomachs of unimmunized or intranasally immunized C57BL/6 mice were quantitatively cultured 3 days and 1, 2, 4, 8, 16, 32, and 52 weeks after challenge withH. pylori. At 3 days and 1 week after challenge, colonization was the same in the immunized and unimmunized mice. By 2 weeks after challenge, the immunized mice had a >2-log decrease in bacterial load, and at all later time points, they either were culture negative or had at least a 2-log decrease in bacterial load. Gastritis in the immunized mice peaked at 1 to 2 weeks after challenge and was characterized by a mixed inflammatory infiltrate and epithelial proliferation centered at the transition between corpus and antrum. By 52 weeks postchallenge, the gastric histology in the immunized mice was not different from that in control unchallenged mice. The unimmunized group began to show a reduction in bacterial load as early as 16 weeks after challenge, and by 52 weeks seven of eight unimmunized mice had developed gastritis and reduced bacterial loads. These results indicate that prophylactic immunization does not prevent colonization byH. pyloribut enables mice to clear the infection or significantly reduce the number of colonizing bacteria. The reduction in bacterial load is associated with gastric inflammation that subsides over time.

The contribution of glutamyl transpeptidase (GGT) (γ-glutamyltransferase [EC 2. 3. 2. 2]) to Helicobacter pylori virulence was investigated in piglets and mice using GGT-deficient isogenic strains. All animals became colonized. However, the bacterial load was significantly lower for mutant bacteria than for parent strains. These results suggest that GGT activity provides an advantage to H. pylori in colonization.

Effective antimicrobial therapies have been developed to treat Helicobacter pylori that, with proper compliance, are more than 85% successful. Individual and population-based problems with pharmaceutical treatment, however, support a role for vaccination in the control of H. pylori infection. Current therapies require the patient to ingest multiple agents several times a day for at least 1 week. 77 Treatment can be accompanied by nausea, diarrhea, abdominal pain, and pseudomembranous colitis. 5,73 These adverse effects contribute to patient noncompliance and reduce the efficacy of the therapy. Additionally, these therapies are prohibitively expensive in developing nations where H. pylori infection is endemic with rates of infection as high as 80% to 90%. Widespread treatment of H. pylori could also result in the development of antibiotic resistant strains that have already been observed in patients treated with triple therapy in whom infection was not cured. 52,66 Additionally, antibiotic cure does not result in protective resistance to subsequent reinfection with H. pylori. It has been reported that successfully treated patients can become reinfected by accidental endoscopic transmission. 66 Finally, pharmaceutical therapies do not address the particular need of those nonsymptomatic individuals who might go on to develop gastric adenocarcinoma caused in part by H. pylori infection. 16 Despite the fact that individuals chronically infected with H. pylori mount a robust humoral immune response, several laboratories have demonstrated the efficacy of prophylactic and therapeutic immunization to prevent or cure H. pylori infection (see later discussion). Childhood vaccination could, in theory, provide an inexpensive and convenient solution to prevent adult gastritis and peptic ulcer disease and reduce the incidence of gastric cancer later in life.

Since the isolation and culture of Helicobacter pylori less than 20 years ago, the terms diffuse chronic active gastritis and multifocal atrophic gastritis have been introduced in an effort to explain the fundamental role this organism plays in the development of gastroduodenal disease1. A number of epidemiological studies have also demonstrated that once this infection is acquired it is rarely cleared, and persists for the life of the individual2. In addition to gastritis and peptic ulcer disease, chronic long-lasting H. pylori infection, particularly when acquired in childhood, can significantly increase the risk of developing gastric cancer3. These studies were so compelling that in 1994 the World Health Organization classified H. pylori as a human carcinogen4. Unfortunately, most epidemiological studies of H. pylori infection have been performed in adults, who were probably infected for decades prior to the diagnosis. Therefore, very little information is available regarding the natural history of the acute phase of the infection.

Immunization can prevent or cure an otherwise chronic helicobacter infection in several animal models despite the chronic nature of natural helicobacter infections. Differences in the antigenic specificity of the antibodies may contribute to the protection observed in these experimental animals. The goal of the present study was to compare the local and systemic antibody responses of humans with chronicHelicobacter pyloriinfection with those of an individual with spontaneous resolution of infection to find an immunological correlate of protection. Spontaneous resolution of infection was accompanied by a change in immunoblot profiles. Whereas a broad range ofH pyloriantigens was recognized in chronically infected patients (including the patient who ultimately cleared the infection spontaneously), resolution of infection in the absence of therapeutic agents resulted in the recognition of only several immunodominant antigens. The most dominant antigen was approximately 66 kDa in molecular mass. Immunoblot analysis demonstrated that these antibodies were specific for the structural subunits of the urease enzyme. These studies suggest that the success of antihelicobacter immunization may be due to the ability of vaccination to induce an immune response against antigens that are normally not immunodominant during the course of infection.

Immunization can prevent or cure an otherwise chronic gastric Helicobacter infection in several different animal models. The goal of the present study was to compare the titers and specificities of local and systemic antibody responses generated by Helicobacter infection and immunization. Protective immunization results in levels of specific gastric antibody significantly lower than induced by infection. However, antibodies from protectively immunized mice preferentially recognize immunodominant proteins of 10-22 and 30 kDa. Immunoblot analysis of infected mice and humans demonstrated that the serum IgA, but not serum IgG, binding profiles yield an accurate profile of the antigenic specificity of the host's gastric IgA. Therefore, serum IgA may be useful in evaluating the immunodominant antigens at the gastric mucosa of infected persons and possibly in determining the immunogenicity of orally applied Helicobacter vaccines.

Infection of humans by Helicobacter pylori can have various outcomes (Fig. 1). In virtually all cases a state of chronic/active gastritis results from an infection by H. pylori, but whether this gastritis progresses to more severe disease states such as duodenal or gastric ulcers or serves as a precursor to gastric cancer appears to be Influenced by both the host response and bacterial virulence determinants. Bacterial virulence factors have been reviewed elsewhere in this volume (“Mechanisms of Helicobacter pylori Infection: Bacterial Factors”); this chapter focuses on the host response to Helicobacter infections in the context of these virulence factors.

Helicobacter pylori has been implicated in the etiology of peptic ulcer disease, chronic gastritis, gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Although significant progress has been made in treating this infection with combinations of either antimicrobial agents or antimicrobial agents plus proton pump inhibitors, these antimicrobial-based treatments continue to be suboptimal. Over the past few years it has become increasingly recognized that direct mucosal immunization can induce protection from infection at mucosal surfaces. Therefore, prevention of H. pylori infection by oral immunization is an alternative approach for the control of H. pylori disease. Using the Helicobacter felis mouse model or H. pylori mouse model, both prophylactic and therapeutic oral immunizations have been shown to be effective against H. pylori. In addition, several H. pylori proteins have been identified as potential candidate vaccines, and a phase 1 clinical trial has been completed that demonstrates the safety and tolerability of urease as a vaccine antigen. Such antigens in combination with a safe mucosal adjuvant could be used in the form of an oral vaccine administered during childhood before exposure to H. pylori to prevent infection. In addition, therapeutic immunization alone or as an adjunct to antimicrobial therapy may be capable of achieving a cure rate approaching 100%.

BACKGROUND & AIMS: Previous findings suggest that TH1 cellular immune responses contribute to Helicobacter-associated gastritis. To further investigate this issue, interleukin 4 gene targeted mice were infected with Helicobacter felis, and a series of adoptive transfer experiments was performed to evaluate the role of both TH1 and TH2 cells. METHODS: Antigen-specific spleen cells from immunized/challenged or nonimmunized/infected mice or CD4+ T-cell lines were transferred adoptively into naive recipients before live bacterial challenge. RESULTS: Transfer of cells from both groups of donors as well as TH1 or TH2 cell lines exacerbated gastric inflammation in the recipients. No effect on bacterial load was observed in recipients of bulk spleen cells from infected mice or recipients of TH1 cell lines. In contrast, when either a TH2 cell line or bulk cells from immunized challenged mice were transferred adoptively, recipients showed a dramatic reduction in bacterial load. Increased numbers of bacteria were also noted in interleukin 4-deficient mice. CONCLUSIONS: These data suggest a differential contribution of TH1 and TH2 cell-mediated immune responses in Helicobacter infection: one associated with the pathogenesis of disease (TH1 phenotype) and the other associated with protection from or control of infection (TH2 phenotype). (Gastroenterology 1997 Dec;113(6):1848-57)

Olestra, a dietary fat substitute, was recently made available to consumers in savory snacks in three cities. Early reports of gastrointestinal complaints attributed to olestra attracted media coverage and fostered confusion among physicians and consumers about the nature of olestra and its effects on the digestive system. We reviewed all published studies of olestra's gastrointestinal effects and all relevant unpublished studies submitted to the Food and Drug Administration. Each study was analyzed by a group of expert gastroenterologists and epidemiologists. The symptoms reported with olestra ingestion are similar to those reported with ingestion of fiber and sorbitol, although the mechanisms involved in changing stool characteristics differ among these food additives. Olestra's effects on stool habit and characteristics are due to its presence in the stool. Large amounts are more likely to induce gastrointestinal symptoms than small amounts. There is no evidence that olestra induces pathological change in bowel function: there is no increased fluid or electrolyte nor is there altered gastrointestinal motility or microflora. Olestra and triglyceride ingestion resulted in a similar frequency of symptoms in normal adults and children and in people with chronic inflammatory bowel disease in remission. Olestra traverses the digestive tract intact to become a stool additive. Some subjects develop a change in bowel habit and stool characteristics due to the presence of more olestra in the stool. These changes resemble those associated with ingestion of sorbitol and fiber.

Publisher Summary Gastric diseases ranging from gastritis and ulcers to adenocarcinoma have historically been major health concerns which afflict millions of people worldwide. Recent work involving a novel bacterial pathogen, Helicobacter pylori, suggests that this microorganism plays an etiologic role in the development of gastric disease. Helicobacter pylori requires a microaerophilic environment for culture, and is associated with the gastric epithelium of man. Despite a number of reports confirming spiral organisms associated with the presence of gastritis and ulcers, the medical community remained skeptical regarding the etiologic role this microorganism played in the development of gastroduodenal disease. A number of laboratories have begun to study the feasibility of prophylactic and therapeutic vaccination for the prevention and treatment of H. pylori infection. The animal models that most investigators have used to investigate H. pylori vaccination is an adaptation of the germ-free/H. felis mouse model. Originally, this model employed 6-week-old germ-free outbred Swiss–Webster mice and has since been adapted for conventional inbred strains of mice.

Experiments were performed to determine the antigenic specificity of a monoclonal antibody (immunoglobulin A [IgA] 71) previously demonstrated to neutralize the ability of Helicobacter felis to colonize mice. Immunoprecipitation of radiolabeled H. felis outer membrane proteins with IgA 71 revealed specificity for a 62-kDa protein. Another of our monoclonal antibodies, IgG 40, precipitated a protein of similar molecular weight. IgA 71 but not IgG 40 also precipitated purified recombinant H. pylori urease. The antigenic specificity of both antibodies was confirmed to be urease by the ability of each to select Escherichia coli clones expressing the H. felis urease genes. The two antibodies were shown to bind nonoverlapping epitopes in a competition enzyme-linked immunosorbent assay. Both IgA 71 and IgG 40 could effectively neutralize H. felis infectivity by incubating the bacteria with the antibodies prior to oral administration to naive mice. The mechanism of protection does not appear to be inhibition of urease activity, as IgA 71 does not inhibit the conversion of urea to ammonia by H. pylori urease in vitro. These results support a protective role for the secretory humoral immune response in Helicobacter immunity and provide further evidence that the urease enzyme can serve as a protective antigen.

Immunodeficient (SCID) and immunocompetent mice were infected with Helicobacter felis to address the role of autoimmunity in Helicobacter-associated gastritis. The extents of inflammation were equivalent in the two groups. The numbers of H. felis organisms were marginally increased in the SCID mice but did not achieve statistical significance. These results indicate that autoimmunity is not necessary to induce disease and that the presence of an adaptive immune system does not significantly affect H. felis colonization.

Polymerase chain reaction (PCR) is a sensitive molecular method that can detect very small amounts of DNA. DNA is a highly stable molecule that can survive in the environment even when the host organism is no longer viable. PCR therefore promises to be a powerful tool for diagnosis of H. pylori infection.

The in vitro activity of trospectomycin, pirlimycin, mirincamycin and N-demethyl clindamycin was measured against 46 clinical isolates of Helicobacter pylori using an agar dilution technique. The MIC50 and MIC90 were 4 and 64 micrograms/ml for pirlimycin and N-demethyl clindamycin, and 32 and 128 micrograms/ml for mirincamycin, respectively. All 46 strains were sensitive to trospectomycin with an MIC50 of 8 micrograms/ml and an MIC90 of 16 micrograms/ml. Of seven strains with the highest trospectomycin MICs (8 or 16 micrograms/ml) 100% were found to be resistant to metronidazole. Among ten strains with low trospectomycin MICs (2 micrograms/ml or less) 100% were sensitive to metronidazole. Possible explantations for the apparent correlation between the MICs of the two drugs are discussed. Since all metronidazole resistant strains were sensitive to trospectomycin, this drug may be useful in treating infection with metronidazole resistant Helicobacter pylori.

QuickVue is an enzyme immunoassay test for qualitative detection of serum immunoglobulin-G antibodies to Helicobacter pylori. We evaluated its ability to predict infection by H. pylori in 100 adult and 49 pediatric patients referred for gastric endoscopy. A patient was defined as infected with H. pylori if either culture or histology was positive. Of the 100 adult patients, 64 had H. pylori infection and QuickVue correctly identified 59 of the 64. Of 36 H. pylori-negative patients, 20 were correctly identified as negative by the test. In this sample of patients, QuickVue had a sensitivity of 92% and a specificity of 56%. In the 49 pediatric patients, QuickVue correctly identified nine of 11 infected cases and 34 of 38 noninfected patients. In this group, the sensitivity was 82% and the specificity was 89%. Overall the test had a sensitivity of 91% and a specificity of 73%. The positive predictive value was 77% and the negative predictive value was 89%.

Helicobacter pylori infection of human gastric epithelium has been associated with gastritis, ulcers and gastric cancers. In an H. felis, germ-free mouse model of infection, oral immunization with bacterial antigens plus cholera toxin resulted in elevated serum, gastric and intestinal anti-H. felis antibody titres and protection from acute infection. Mice given monoclonal IgA anti-H. felis antibody at the time of initial challenge were also protected from infection. These results demonstrate that oral vaccination may be a feasible approach for the prevention of H. pylori infection of humans.

In this study, the systemic immune response to bacterial cell sonicates of Helicobacter pylori was characterized in children with symptomatic gastroduodenal disease. Isotype-specific antibodies to H. pylori in samples of serum from 16 children with culture-proven disease caused by H. pylori and from 19 controls with negative cultures were measured by ELISA with bacterial cell lysates. The levels in serum of IgA antibody to cell sonicates of H. pylori were significantly higher in the patients with positive cultures than in the controls. Only 45% of patients were infected when the established optical density cutoff was used to discriminate between patients infected and not infected with H. pylori. Levels of IgM antibody in serum were not significantly higher in patients who were infected with H. pylori. On the basis of this survey and of previous work conducted in our laboratory, we conclude that at a serum dilution of 1:800, IgG but not IgA or IgM antibody to H. pylori is useful in the rapid screening of symptomatic children for the presence of H. pylori.

Helicobacter pylori, which has been associated with gastritis and duodenal ulcers, commonly chronically infects adults. Eradication of this microorganism, which is difficult to achieve, results in normalization of gastritis and marked reduction in the relapse rate of duodenal ulcers. Since eradication is difficult to achieve, prevention of initial colonization of the gastrointestinal tract may be a viable alternative for abrogation of H. pylori-associated gastroduodenal disease. To test the feasibility of this approach, mice and ferrets were orally immunized with killed H. pylori. Immunization induced immunoglobulin A and G anti-H. pylori antibodies in both gastrointestinal secretions and sera of mice. These responses were enhanced when cholera toxin was included in the immunization protocol as a mucosal adjuvant. In ferrets, addition of cholera toxin resulted in significant enhancement of anti-H. pylori antibody levels in sera and intestines. Thus, oral immunization with killed H. pylori may be feasible approach to protect hosts from this infection and the accompanying gastroduodenal disease.

See article on page 335 Helicobacter pylori is considered one of the most common pathogenic infections of mankind. Despite its worldwide distribution, the pathogenesis of H pylori associated gastroduodenal disease remains poorly understood. What is clear is that only a minority of infected individuals develop severe inflammation leading to peptic ulcers or gastric cancer, the more severe manifestations of helicobacter infection. What are the factors which determine whether an infected individual will develop severe disease? It has been suggested that phenotypic or genotypic differences among bacterial isolates may be important in disease.1 There is evidence to suggest that individuals infected with strains of H pylori which express the cytotoxin associated gene product CagA, a marker for the presence of a “pathogenicity island”, are more likely to develop peptic ulcers or gastric cancer.2-5Recent observations suggest that polymorphism of vacA genotypes may determine whether an H pylori infected individual develops gastritis or an ulcer.6 However, only a small fraction of the estimated 60% of all individuals infected with such strains of H pylori develop severe gastroduodenal disease (peptic ulcers or gastric cancer). This suggests that …

There is a strong association between chronic gastroduodenal disease in adults and children and the recovery of Helicobacter pylori (formerly Campylobacter pylori) from gastric biopsy specimens. However, data relevant to host defense mechanisms directed against this organism are scarce. The ability of H. pylori-specific antibody and complement to enhance the in vitro phagocytosis and killing of H. pylori by human peripheral blood polymorphonuclear leukocytes (PMNL) were studied. Sera with IgG antibody to H. pylori from five children with culture-proven H. pylori gastric disease markedly enhanced complement-dependent phagocytosis of H. pylori in an assay using flow cytometry to measure uptake of fluorescent-labeled bacteria by PMNL. Absorption of specific antibody from patient sera with an excess of H. pylori organisms completely abrogated this enhancement. IgG purified from plasma with high IgG antibody titers to H. pylori enhanced complement-dependent phagocytosis of H. pylori and increased the killing of this organism by PMNL in the presence of 5% human opsonic complement by one full log. IgG antibody to H. pylori appears to be highly functional in vitro in promoting complement-dependent phagocytosis and killing of H. pylori by PMNL.

In 1984, Marshall and Warren [10] reported the presence of spiral organisms in the gastric mucosa of adults with gastritis. Since then, this organism has been isolated and characterized as Helicobacter pylori (H. pylori). A number of investigators have reported an association between H. pylori and gastritis or gastric and duodenal ulcers in adults [6, 7, 13]. With the advent of small flexible fiber-optic endoscopes, several pediatric studies have investigated the relationship of H. pylori infection and gastritis [2–4]. In industrialized countries, H. pylori infection is a rare finding in the gastric mucosa of children. The low prevalence as well as the lack of confounding variables such as smoking, alcohol intake, or use of nonsteroidal antiinflammatory drugs (NSAIDS) in children may allow such pediatric studies of clarify the role of H. pylori in the pathogenesis of gastritis and gastric or duodenal ulcers. The purpose of the present study was: (a) to determine the relationship between H. pylori and gastritis or peptic ulcer disease in children and (b) to determine the natural history of H. pylori in children with gastritis.