Paternal and maternal infection status and Helicobacter pylori in their children.
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Biomedical subjects
Publications and source records attributed to F Pallone.
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BACKGROUND: Celiac disease is frequently associated with chronic gastritis. Helicobacter pylori is the main etiologic agent of chronic gastritis. The aim of this study was to assess the prevalence of H. pylori, the related symptoms, and the endoscopic and histologic gastric features in children with celiac disease. METHODS: Eight-one (24 boys, 57 girls; age range: 1.4-17.7 years, median 6.8) children with celiac disease were studied. All children had a blood sample taken. In a subgroup of 30 children who underwent endoscopy, three gastric biopsy specimens were taken for histology (hematoxylin and eosin, Giemsa, immunohistochemistry) and urease quick test. Symptom complaints were recorded. Age- and sex-matched (one case, one control) children without celiac disease were used for comparison. Serum H. pylori IgG were measured by means of a locally validated commercial enzyme-linked immunoassay. RESULTS: Overall, 15 of 81 (18.5%) children with celiac disease and 14 of 81 (17.3%) control children were positive for H. pylori. The percentage of H. pylori positivity was similar in children with untreated and treated celiac disease. Recurrent abdominal pain was the only symptom that helped to distinguish between H. pylori-positive and H. pylori-negative children. However, symptoms disappeared in patients with celiac disease after gluten withdrawal, irrespective of H. pylori status. All endoscopic (erythema, nodularity) and histologic (superficial-, interstitial-, lymphocytic-gastritis, activity, lymphoid follicles) findings did not differ between celiac and nonceliac H. pylori-positive children. CONCLUSIONS: Prevalence and clinical expressivity of H. pylori infection is not increased in children with celiac disease. The clinicopathologic pattern of the infection is not specifically influenced in this condition.
BACKGROUND: Little information is available about the relationships between Helicobacter pylori cytotoxin-associated protein (CagA) and clinicopathologic features in children. The purpose of this study was to test whether determining serum IgG antibodies to CagA is a useful tool for detecting more severe disease. METHODS: One hundred twenty-seven consecutive children (age range, 0.75-17.8 years; median, 9.4 years) referred for gastroscopy were included in the study. Antral and corpus biopsies were taken for gastric histology and H. pylori detection. Major symptoms and endoscopic findings were recorded. A serum sample was drawn from each child and assayed for IgG antibodies CagA by a commercial enzyme-linked immunosorbent assay. RESULTS: Sixty-three (50%) children had no evidence of H. pylori infection, 28 (22%) were H. pylori positive/CagA positive, and 36 (28%) were H. pylori positive/CagA negative. There were no differences in clinical diagnosis and occurrence of any predominant symptom according to H. pylori and CagA status. Findings of antral nodularity were more frequent (p = 0.003) in H. pylori-positive/CagA-positive children than in H. pylori-positive/CagA-negative children. The gastritis score was significantly higher in H. pylori-positive/CagA-positive children than in H. pylori-positive/CagA-negative children (5.7 +/- 1.9 vs. 3.8 +/- 1.6, respectively; p = 0.0003), either in the antral (p = 0.0002) or in the corpus (p = 0.001) mucosa. Inflammation (p = 0.0001) and activity (p = 0.0001) scores were both higher in H. pylori-positive/CagA-positive children than in H. pylori-positive/CagA-negative children, but the H. pylori density score was not significantly different (p = NS). In no case was normal gastric mucosa found in H. pylori-positive/ CagA-positive children. Lymphocytic gastritis (p = 0.0008) and lymphoid follicles (p = 0.000003) were a more frequent finding in H. pylori-positive children than in H. pylori negative children, irrespective of CagA status. CONCLUSION: Testing for serum IgG to CagA detects higher grades of gastric inflammation among children with H. pylori infection. It may be useful in targeting H. pylori-positive/ CagA-positive children for antimicrobial therapy while reducing the need for endoscopy and gastric biopsy.
Transcripts for interleukin (IL) 15 were detected in the gastric mucosal samples of 5/5 (100%) patients with no evidence of Helicobacter pylori infection and in 4/14 (28%) H. pylori-infected patients (P< 0.05). Both IL-15 mRNA and IL-15 protein were detected in 1/6 (17%) patients who successfully underwent H. pylori eradication therapy, before treatment and in 5/6 (83%) cases after eradication. Even though a parallel significant (P < 0.03) improvement of gastritis score occurred after eradication, the severity of gastritis did not differ according to the mucosal IL-15 expression among H. pylori-infected patients, irrespective of the CagA serology. This study demonstrates, for the first time, that transcripts for IL-15 are expressed in the human gastric mucosa. Changes occurring during H. pylori colonisation and after eradication raise the hypothesis that H. pylori may down-regulate IL-15 expression in the gastric mucosa.
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BACKGROUND & AIMS: Autoantibodies against tropomyosins (TMs) have been reported in ulcerative colitis (UC). In this study the hTM isoforms (hTM1-5) present in intestinal epithelial cells and in smooth muscle were investigated, and the immunoreactivity against hTMs by immunoglobulin G (IgG) produced in vitro by colonic mucosal lymphocytes (LPMCs) from patients with UC, Crohn's disease (CD), and controls was examined. METHODS: TMs were extracted from colonic and jejunal epithelial cells and smooth muscle, and hTM isoforms were identified using isoform-specific monoclonal antibodies by enzyme-linked immunosorbent assay and transblot analysis. The immunoreactivity of IgG produced by colonic LPMCs was analyzed against the recombinant hTM isoforms. RESULTS: The major hTM isoforms present in colonic and jejunal epithelial cells are hTM5 and hTM4, whereas intestinal smooth muscle contains the hTM1-3 isoforms. The IgG synthesized in vitro by LPMCs from UC (n = 19) recognized hTM5 and hTM1, more significantly (P < 0.04 to <0.001) when compared with CD (n = 12) and controls (n = 17). However, IgG produced by LPMCs from CD did not show such anti-hTM reactivity. Mucosal anti-hTM IgG mainly belonged to the IgG1 subclass. CONCLUSIONS: Intestinal epithelial cells and smooth muscle have distinct hTM isoforms. Patients with UC, and not CD, show mucosal autoantibody response against hTM isoforms, particularly hTM5 and hTM1.
In this study the seroepidemiology of H. pylori and Epstein-Barr virus was compared in the same setting. A sample of 705 subjects completed a structured questionnaire. A serum sample was drawn from each subject and assayed for H. pylori IgG. Antibodies to Epstein-Barr virus were determined in a subgroup of 466 subjects. Cross-tabulation of data showed that 274 (58.8%) subjects were seropositive and 20 (4.3%) were seronegative for both infections, 17 (3.6%) were seropositive for H. pylori, and 155 (33.3%) were seropositive for Epstein-Barr virus (odds ratio=2.08, 95% confidence interval: 1.008-4.3). Nevertheless, the agreement between H. pylori and Epstein-Barr virus seropositivity was no better than chance (kappa=0.067) and the age-related seroprevalence curve of Epstein-Barr virus was similar in H. pylori seropositive and seronegative subjects. Furthermore, multiple logistic regression analysis did not show any risk factor shared by both infections. The findings of this study do not support the hypothesis that H. pylori and Epstein-Barr virus share a common mode of transmission. It can be speculated that the oral cavity may not be an important reservoir for H. pylori.
Autoimmunity to cytoskeletal protein tropomyosin (TM) has been demonstrated in UC. However, the TM isoforms involved in this IgG-mediated autoimmune response in UC and the possible presence of serum IgG antibodies against TM (hTMs IgG) in unaffected UC relatives are unknown. The aim of this study was to investigate the human TM (hTM) isoforms recognized by serum IgG from UC and to explore whether hTM IgG antibodies are present in healthy UC relatives. We studied 33 UC patients with 58 unaffected relatives, 31 Crohn's disease (CD) patients with 31 unaffected relatives and 20 controls (C). Serum IgG against four recombinant hTM isoforms (hTM1, 2, 3, 5) were tested by ELISA. p-ANCA were tested by ELISA and immunofluorescence. Serum hTM1 and hTM5 IgG were higher in UC patients than in CD and C (P<0.005). Among UC patients 52% were seropositive for hTM1 and 64% for hTM5 (P<0.001 versus CD and C). In UC, hTM5 IgG were higher in p-ANCA+ than in ANCA- patients (P=0.04). In UC relatives hTM1 IgG were higher than in CD relatives and C (P<0.01). UC relatives were more frequently seropositive for hTM1 than hTM5 IgG (P=0.001). while probands were more frequently seropositive for hTM5 IgG (P=0.008). We conclude that autoimmunity to hTMI and hTM5 is a feature of UC, while hTM1 IgG differentiate UC relatives from controls. A genetic susceptibility to immune recognition of hTM isoforms in UC is suggested.
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BACKGROUND/AIM: Interleukin (IL) 12 is involved in the mucosal response during intestinal inflammation but its role is not fully understood. The response of human lamina propria T lymphocytes (T-LPL) to IL-12 in terms of interferon gamma (IFN-gamma) release and proliferation was investigated, exploring whether IL-15 and IL-7 cooperate with IL-12. The role of accessory molecules (CD2 and CD28) was also investigated. METHODS: Unstimulated and phytohaemagglutinin preactivated T-LPL cultures were incubated with or without the initial addition of cytokines, anti-CD2 or anti-CD28 antibodies. IFN-gamma mRNA was detected by reverse transcriptase polymerase chain reaction, and protein secretion was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: IFN-gamma mRNA was induced in T-LPLs by IL-12 and IL-15 but not IL-7, whereas IFN-gamma was measured only in IL-12 stimulated T-LPL cultures. IL-12 induced IFN-gamma release was not abrogated by neutralising anti-IL-2 antibody or by cyclosporin A. IL-12 synergised with either anti-CD2 or anti-CD28 antibodies in inducing IFN-gamma synthesis. In preactivated T-LPLs, IL-7 enhanced IFN-gamma release induced by both IL-12 and anti-CD2, whereas IL-15 potentiated only IL-12 induced IFN-gamma synthesis. IL-12 did not induce proliferation of either unstimulated or preactivated T-LPLs and it did not enhance the CD2/CD28 stimulated T-LPL proliferative response. No transcript for IL-12 receptor beta1 subunit was detected in freshly isolated and activated T-LPLs whereas the beta2 subunit mRNA was consistently found in T-LPL samples. CONCLUSIONS: IL-12 induces human T-LPLs to produce and release IFN-gamma, and IL-15 and IL-7 cooperate with IL-12 in expanding the IFN-gamma mucosal response.
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BACKGROUND AND AIMS: Mucosal and systemic antibodies against Helicobacter pylori have been detected but their role in the natural history of Helicobacter pylori-related diseases is unclear. In this study, the levels of Helicobacter pylori IgG and IgA were related to the grade of gastritis. PATIENTS AND METHODS: A series of 152 dyspeptic patients underwent gastroscopy with biopsies. Helicobacter pylori was detected in 131 (86%) patients. Samples of serum and unstimulated saliva were collected. Helicobacter pylori IgG and IgA were measured in homogenised gastric biopsies, saliva and serum by an in-house enzyme linked immunosorbent assay. RESULTS: Levels of gastric mucosa, salivary and serum Helicobacter pylori IgG were higher (p < or = 0.01) in Helicobacter pylori positive than negative patients. Likewise, levels of gastric mucosa and serum Helicobacter pylori IgA were higher (p < 0.01) in Helicobacter pylori positive patients. Gastric mucosa, saliva and serum Helicobacter pylori antibody levels did not differ between superficial and atrophic, active and inactive Helicobacter pylori positive gastritis. CONCLUSIONS: These data indicate that gastric inflammatory changes may not necessarily be related to the antibody response against Helicobacter pylori.
AIM: The purpose of this study was to investigate the behavior of circulating endothelin-1, a vasoconstrictor and mitogenic peptide, in patients with inflammatory bowel disease. PATIENTS: We investigated plasma endothelin-1 levels in 29 patients with Crohn's disease, 13 with ulcerative colitis and 26 healthy subjects as controls. METHODS: Erythrocyte sedimentation and C-reactive protein were also measured in all patients. Plasma endothelin-1 was measured by specific radioimmunoassay and expressed as pg/ml. RESULTS: Both Crohn's disease and ulcerative colitis patients showed a significant increase in plasma endothelin-1 concentration (22.3 +/- 8.2 pg/ml and 11.2 +/- 2.7 pg/ml, respectively) when compared to healthy subjects (6.2 +/- 1.5 pg/ml). Moreover, plasma endothelin-1 levels were significantly higher in Crohn's disease patients than those in ulcerative colitis patients (22.3 +/- 8.2 pg/ml vs 11.2 +/- 2.7 pg/ml; p < 0.001, respectively). A weak correlation (r = 0.645; p < 0.013) between erythrocyte sedimentation and endothelin-1 levels was observed in Crohn's disease patients. Age, sex, clinical activity of the disease, duration of history, anatomical localization of disease and therapy had no influence on plasma endothelin-1 levels. CONCLUSION: Our results show that plasma endothelin-1 levels increase in chronic inflammatory bowel disease and mainly in Crohn's disease. This observation leads us on to believe that endothelin-1 has a important role in inflammatory bowel disease.
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BACKGROUND & AIMS: Cell-mediated immunity is a feature of Crohn's disease (CD). The heterodimer interleukin (IL)-12, produced by phagocytes, induces T-cell cytokines, primarily interferon (IFN)-gamma. This study examined whether CD lamina propria mononuclear cells (LPMCs) express and release bioactive IL-12. METHODS: LPMCs were isolated from 13 patients with CD, 9 with ulcerative colitis (UC), and 13 controls. Messenger RNA for p40 and p35 IL-12 subunits was evaluated by reverse-transcription polymerase chain reaction. IL-12 was measured by enzyme-linked immunosorbent assay in LPMC culture supernatants. The INF-gamma-inducing effect of unstimulated LPMC supernatants was evaluated. RESULTS: Messenger RNA for both IL-12 subunits was detected in LPMCs of 11 of 13 patients with CD, 1 of 9 patients with UC, and 1 of 13 controls (P < 0.001). IL-12 was measured (10.5 +/- 2 pg/mL at 24 hours) in unstimulated CD LPMCs and was enhanced by pokeweed mitogen, lipopolysaccharide, and staphylococcal enterotoxin B. No IL-12 was detectable in 8 of 9 patients with UC and 12 of 13 control-unstimulated LPMCs. IL-12 induced by pokeweed mitogen and staphylococcal enterotoxin B in UC was lower than in CD and did not differ from controls. An IFN-gamma-inducing effect was restricted to unstimulated CD LPMC supernatants and was inhibited by an anti-IL-12 antibody in a dose-dependent fashion. CONCLUSIONS: IL-12 transcripts are expressed in CD intestinal tissues. CD LPMCs are up-regulated in their capability of releasing bioactive IL-12. Expression and release of bioactive IL-12 seem to differentiate CD from UC.
Peripheral blood monocyte-derived multinucleated giant cells are a well-known feature of chronic inflammatory conditions. Similarly, virus-induced syncytia derived from CD4+ cells are considered to be typical of human immunodeficiency virus infection under culture conditions. Here, Stefano Fais and colleagues summarize recent experimental results comparing the mechanisms underlying the formation and fate of these two different polykaryons, discussing their putative role in the immune response.
The usefulness of 99mTc-HMPAO scintigraphy in the early detection of postoperative recurrence of Crohn's disease was evaluated in 17 patients undergoing ileocecal resection and prospectively followed up for one year. Scintigraphy was performed 6 and 12 months after surgery and recurrence assessed by colonoscopy within two weeks. As controls, four patients with ileocecal resection for cecal carcinoma were studied. To perform scintigraphy, autologous granulocytes were labeled with 99mTc-HMPAO, injected, and tau-camera images acquired after 30 min and 3 hr. Six months after surgery, 4/8 Crohn's disease patients showed endoscopic recurrence, and 30-min scintigraphy was positive only in these four patients (four true positives, four true negatives). At 12 months, endoscopic recurrence was detected in 10/14 Crohn's disease patients, and 30-min scintigraphy was positive in 9/14 patients (eight true positives, three true negatives, two false negatives, one false positive). Scintigraphy at 3 hr showed a lower specificity in detecting CD recurrence both at 6 and 12 months. The endoscopic and 30-min scintigraphic score were significantly correlated both at 6 and 12 months (P = 0.007; P = 0.04). Scintigraphy was negative in 4/4 controls at 30 min (four true negatives) and positive in 1/4 (one false positive) at 3 hr. We conclude that 99mTc-HMPAO scintigraphy at 30 min is a sensitive technique for the early detection of Crohn's disease recurrence in patients under regular follow-up after surgery.
An in-house enzyme-linked immunosorbent assay (ELISA) for measurement of Helicobacter pylori-specific immunoglobulin G (IgG) and IgA in saliva was evaluated by comparison with histopathologic (Giemsa staining) and biochemical (urease quick test) examination of gastric biopsy specimens obtained from 112 children referred for diagnostic gastroscopy. Serum H. pylori IgG was also measured in a subgroup of 50 children by the same ELISA. Salivary H. pylori IgG levels were significantly higher in H. pylori-positive (n = 57) than in H. pylori-negative (n = 55) children (P < 0.001). The sensitivity and specificity of the salivary IgG test were 93 and 82%, respectively; the positive and negative predictive values were 84 and 92%, respectively; and the accuracy was 87.5%. Salivary H. pylori IgA did not distinguish H. pylori-positive from H. pylori-negative children. The performance of serum H. pylori IgG was slightly (3 to 6%) better than that of salivary H. pylori IgG. The salivary IgG test can be considered a useful tool for the screening of H. pylori infection in children.