Lea Irene Veijola, Aino Mirjam Oksanen, Herttoniemi Hospital, City of Helsinki, Kettutie 8, 00800 Helsinki, Finland
Lea Irene Veijola, Hilpi Iris Kaarina Rautelin, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmanink. 3, 00014 Helsinki, Finland
Pentti Ilmari Sipponen, Repolar Oy, Box 26, 02101 Espoo, Finland
Hilpi Iris Kaarina Rautelin, HUSLAB, Helsinki University Central Hospital Laboratory, Haartmanink 3, 00014 Helsinki, Finland; Department of Medical Sciences, University of Uppsala, Dag Hammarskjölds väg 17, SE-75185 Uppsala, Sweden
Author contributions: Veijola LI, Rautelin HIK and Oksanen AM planned the study; Veijola LI and Oksanen AM interviewed and examined the patients, and performed the gastroscopies; Sipponen PI examined the histology of the biopsy materials; Veijola LI analyzed the data; Veijola LI and Rautelin HIK wrote the article; all authors participated in the revision of the manuscript.
Correspondence to: Lea Irene Veijola, MD, PhD, Herttoniemi Hospital, City of Helsinki, Kettutie 8, 00800 Helsinki,
Telephone: +358-9-3105511 Fax: +358-9-19126382
Received: September 27, 2009 Revised: November 16, 2009
Accepted: November 23, 2009
Published online: January 7, 2010
AIM: To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis.
METHODS: Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology, immunoblot-based serology, and histology to reveal a past or a present H. pylori infection. In addition, serum markers for gastric atrophy (pepsinogen Ⅰ, pepsinogen Ⅰ/Ⅱ and gastrin) and autoimmunity [parietal cell antibodies (PCA), and intrinsic factor (IF), antibodies] were determined.
RESULTS: Of the 14 patients with severe gastric atrophy, as demonstrated by histology and serum markers, and no evidence for an ongoing H. pylori infection, eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with severe corpus atrophy, PCA and IF antibodies were detected in four. Among the patients with low to moderate grade atrophic gastritis (all except one with an ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity were seldom detected. However, one H. pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis.
CONCLUSION: Signs of H. pylori infection in autoimmune gastritis, and positive autoimmune serum markers in H. pylori gastritis suggest an etiological role for H. pylori in autoimmune gastritis.
© 2010 Baishideng. All rights reserved.
Key words: Helicobacter pylori; Autoimmune gastritis; Gastric atrophy; Vitamin B12 deficiency
Peer reviewers: Cuong D Tran, PhD, Research Fellow, Affiliate Lecturer, University of Adelaide, Gastroenterology Unit, Children, Youth and Women’s Health Service, 72 King William Rd, North Adelaide, SA 5006, Australia; Dr. T Choli-Papadopoulou, Associate Professor, Department of Biochmeistry, Aristotle University of Thessaloniki, School of Chemistry, Thessaloniki 55124, Greece
Veijola LI, Oksanen AM, Sipponen PI, Rautelin HIK. Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori infection. World J Gastroenterol 2010; 16(1): 83-88 Available from: URL: http://www.wjgnet.com/1007-9327/full/v16/i1/83.htm DOI: http://dx.doi.org/10.3748/wjg.v16.i1.83
Autoimmune type corpus gastritis, formerly named type A gastritis, is severe atrophy of gastric corpus associated with hypochlorhydria. Even without total gastric atrophy, many of these patients have an inability to absorb vitamin B12 from food. Generally, 15%-20% of vitamin B12 malabsorption in elderly patients is due to pernicious anaemia, as defined as deficiency of intrinsic factor (IF). Over 90% of patients with pernicious anaemia have parietal cell antibodies (PCA) and 50%-70% have elevated IF antibodies. The autoantigen for PCA is H+/K+-adenosine triphosphatase, the proton pump.
In patients with Helicobacter pylori (H. pylori) infection, superficial gastritis proceeds to atrophic gastritis in about half of the patients. Although this type of atrophic gastritis, which is associated with intestinal metaplasia, mainly involves the antrum, it can proceed to the corpus or affect the mucosa focally, viz. multifocal atrophic gastritis. Advanced atrophy develops over many years and H. pylori disappears from the gastric mucosa. In some patients, the antral intestinal metaplasia disappears and PCA appears; thus, the disease resembles classic autoimmune gastritis. Gastric H+/K+-ATPase is also the major autoantigen in chronic H. pylori induced atrophic gastritis in corpus mucosa.
In H. pylori induced atrophic gastritis, the activated CD4+ Th1 cells infiltrating the gastric mucosa cross-recognize the epitopes of the gastric parietal cell proton pump and various H. pylori proteins[8,9]. It is not known if H. pylori is the initiating factor in activating Th1 cells, which leads to inflammation and apoptosis, or is only a coincidental bystander. If the classic autoimmune type gastric atrophy is an end-stage of H. pylori induced gastric autoimmunity with atrophic gastritis, the prevalence of pernicious anaemia should decrease with declining prevalence of H. pylori. It is not known if vitamin B12 malabsorption in the late stages of gastric atrophy could be restored or prevented if H. pylori were eradicated earlier[11-14].
In the present study we investigated the signs of a previous H. pylori infection in patients with different grades of atrophic gastritis to assess the proportion of gastric atrophy not associated with H. pylori infection.
MATERIALS AND METHODS
All patients with an earlier gastroscopy reprint available and who had undergone a gastroscopy for clinical indications at Herttoniemi Hospital during 2004 and 2005 were included in the present study if their follow-up histology indicated they had atrophic gastritis. Twenty-three of the 38 patients with different grades of atrophic gastritis had a blood sample available and were included in the study. The median age was 65 years and 18 were females.
The Ethics Committee of the Hospital District of Helsinki and Uusimaa approved the study and all the participants gave their written informed consent.
Two biopsies from each of the antrum and the corpus were taken during gastroscopy and stained with haematoxylin-eosin, Alcian blue (pH 2.5)-periodic acid Schiff, and modified Giemsa stains. All the samples were examined by one pathologist who was unaware of the identity of the samples. The samples were assessed according to the updated Sydney system.
H. pylori antibodies were detected by an enzyme immunoassay (EIA) and by immunoblotting. Serum samples were taken after gastroscopy and stored (-20℃) until analyzed for IgG antibodies to H. pylori using a locally validated in-house EIA with high sensitivity and specificity. Immunoblotting was performed by MP Diagnostics Helico blot 2.1 (MP Biomedicals, Singapore). The interpretation criteria for an H. pylori seropositive sample, according to the manufacturer, were: (1) fulfilling the criteria for CagA positivity; (2) the presence of any bands at 89 kDa, 37 kDa, or 35 kDa; or (3) the presence of both the bands at 30 kDa and 19.5 kDa. The criteria for CagA positivity were the presence of 116 kDa CagA band (a) in combination with current infection marker CIM; (b) in combination of the 30 kDa (UreA) and 19.5 kDa bands; or (c) in combination of at least one of the following bands 89 kDa (VacA), 37 kDa, or 35 kDa.
PCA were measured by Varelisa (Pharmacia Diagnostics, Freiburg, Germany) using H+/K+-ATPase as an antigen. According to the manufacturer’s instructions, values > 15 U/mL were interpreted as positive but equivocal values (10-15 U/mL) were interpreted negative as well as values < 10 U/mL.
Serum IF antibodies of the blocking type were measured routinely with the haemoglobin charcoal adsorption assay. The cut off value used was 2 U/L.
Serum pepsinogen Ⅰ and Ⅱ and gastrin-17 levels were investigated with Gastropanel (Biohit PLC Diagnostics, Helsinki, Finland). The reference ranges were 30-120 mg/L for pepsinogen Ⅰ, 3-10 mg/L for pepsinogen Ⅱ, 3-20 for pepsinogen Ⅰ/Ⅱ, and 2-10 pmol/L for gastrin-17.
The differences between the groups were tested using two-tailed Fisher’s exact test and the data were analysed using GraphPad software (QuickCalcs online calculators for scientists www.graphpad.com). P values < 0.5 were considered significant.
Of the 23 patients included in the study, 14 had severe gastric atrophy according both to histology and the serum markers, and the remaining nine patients had mild to moderate atrophic gastritis. The patients with severe atrophy were slightly younger (median age 64 years) than the other patients (median age 70 years). None of the patients with severe atrophy had either H. pylori in histology or elevated H. pylori antibodies in the EIA (Table 1); one patient had had a successful H. pylori eradication therapy 7 years earlier. Of the nine patients with mild to moderate atrophic gastritis, two had had a successful eradication therapy (4 mo and 6 mo earlier, respectively) and four had an ongoing infection shown in histology; seven had elevated H. pylori antibodies in the EIA (Table 1). All patients, except one with moderate atrophic gastritis, had chronic gastritis in the corpus, whereas the antrum was significantly less often affected in patients with severe atrophy compared to those with mild and moderate atrophic changes (P = 0.04, Fisher’s exact test, Table 1). Antral intestinal metaplasia was not found in any of the patients with severe atrophy.
Serum markers for gastric autoimmunity were only rarely detected in patients with mild to moderate atrophic gastritis (PCA in three patients and IF antibodies in one patient, Table 1). In contrast, all 14 patients with severe atrophy had either elevated PCA or IF antibodies, six patients having both antibodies elevated. Furthermore, the levels of elevated PCA and IF antibodies were higher in patients with severe atrophy (eight of 12 patients with elevated PCA had a PCA titre over 100, and the mean IF antibody titre in eight patients with an elevated value was 8.7) compared to patients with only mild to moderate atrophic changes (only one of the three patients with elevated PCA had a PCA titre over 100 and the IF antibody titre in the only patient with an elevated value was 2.1).
H. pylori antibodies could be demonstrated by immunoblotting in 8/9 patients with mild to moderate atrophic gastritis and in 8/14 patients with severe gastric atrophy (Table 1). Patients with severe atrophy and a positive immunoblot result did not significantly differ from those with severe atrophy and negative immunoblot results as far as age, sex, histological findings, and serum results were concerned (Table 1). Although six patients with severe atrophy showed negative immunoblot results (according to the criteria of the manufacturer) four of them had a positive CagA band in the immunoblot; thus, only two patients showed no evidence of previous H. pylori infection. In addition, one patient with mild atrophic gastritis had no evidence (not even a CagA band) for ongoing or previous H. pylori infection (Table 1). This particular patient showed clearly elevated PCA (> 100 U/mL) and slightly elevated IF antibodies (2.1 U/L).
In our study, of the 14 patients having autoimmune type atrophic gastritis (severe gastric atrophy with elevated PCA and/or IF antibodies) only two had no signs of previous H. pylori infection. In addition, all except one of the patients with mild to moderate atrophic corpus gastritis had an ongoing H. pylori infection or signs of previous infection. The H. pylori negative patient with minor atrophic changes in the gastric corpus had elevated PCA and IF antibodies; whether this particular patient goes on to develop severe gastric atrophy of autoimmune type remains to be shown. To the best of our knowledge, she is the first patient described in the literature as having preatrophic autoimmune gastritis with elevated serum markers of pernicious anaemia and no signs of H. pylori infection, despite being investigated with both invasive and non-invasive methods: antrum and corpus histology in two gastroscopies with a 5.4 years interval and negative EIA serology and immunoblotting, including CagA.
In severe gastric atrophy, the exclusion of previous H. pylori infection is controversial, as the sensitivity of histology is low, and many of the EIA based serological tests are poorly validated. In H. pylori gastritis, the antibodies in EIA serology decline below the cut-off values along with advanced atrophy, as well as after eradication therapy; thus, the previous H. pylori infection cannot be deduced by negative EIA serology. Immunoblotting with CagA antibodies can give positive results for years after the disappearance of H. pylori[22,23], but all H. pylori strains are not CagA positive. Discrepancies in CagA seropositivity yielded by immunoblotting in patients with severe gastric atrophy[24,25] may derive from the different sensitivities of the immunoblotting methods used.
Studies of patients with preatrophic autoimmune type of corpus gastritis are rare. In a population-based study, all 12 patients with autoimmune type atrophic gastritis (diffuse lymphocytic infiltration of the entire lamina propria in the corpus mucosa) without severe gastric atrophy showed H. pylori in histology or serology. In the same study, of the 28 individuals with severe autoimmune type gastric atrophy six were H. pylori positive in histology and another 13 were positive in serology (altogether 68% positive for H. pylori). Considering the moderately high prevalence (2.8% in the Kalixanda study) of the autoimmune type of gastric atrophy in general, the description in the literature of patients with H. pylori negative autoimmune type gastritis in preatrophic stage is rare.
Uibo described a 17-year-old female with no signs of gastritis and H. pylori in histology developing atrophic gastritis during a 12-year follow-up. However, the exclusion of H. pylori infection in this case was based only on histology, and the childhood infection rate in this population cohort was nearly 100%. Kuipers described two patients who were negative for H. pylori and without gastritis at first visit, who then developed atrophic gastritis (one developed also intestinal metaplasia and pernicious anaemia) during more than 10 years of follow-up. However, although in this study the H. pylori infection was assessed with serology and histology at the first visit, in cases of discrepant results, histology was considered predominant over serology unless atrophic mucosa was observed. Whether these two patients had positive serology at the first visit was not mentioned. In the study of Segni et al of children with juvenile autoimmune thyroid disease, of the 18 children with elevated PCA who underwent gastroscopy, two children with hypergastrinaemia had H. pylori negative preatrophic gastritis, as shown by histology and EIA serology. Immunoblotting was not studied and follow-up has not been published. In the study of adult patients with Sjögren’s syndrome, there was no difference in the prevalence of H. pylori infection, antigastric antibodies, or gastric histology between patients and controls, but after successful eradication therapy for H. pylori, the lymphocytic infiltration and atrophy in patients with Sjögren’s syndrome, contrary to the controls, did not improve. In addition, patients with Sjögren’s syndrome who were positive for antigastric antibodies all had H. pylori infection and they more often had atrophic gastritis than the controls. In conclusion, from the previous studies, patients with autoimmune type atrophic gastritis without H. pylori infection might rarely exist, but at the moment a study showing preatrophic gastritis proceeding to total gastric atrophy without H. pylori infection is lacking. This is in accordance with our results; as the patient having preatrophic gastritis without signs of H. pylori infection did not proceed to total gastric atrophy during 5 years of follow-up.
Several studies suggest that autoimmune atrophic corpus gastritis is associated with H. pylori infection in the majority of cases. In one study, two-thirds of patients with atrophic corpus gastritis had evidence of H. pylori infection, when assessed with histology and serology. In another study, 62% of the patients with pernicious anaemia and severe atrophic corpus gastritis had positive H. pylori serology. In one further study, patients with atrophic corpus gastritis were negative for H. pylori in histology and in EIA-serology, but positive when studied by immunoblotting. In another study of atrophic corpus gastritis, among 111 patients with negative H. pylori EIA serology, 95.5% were positive in immunoblotting. In a study of 10 patients with severe atrophic corpus gastritis, all were H. pylori negative in histology and in EIA-serology, and only one was positive in immunoblotting. However, in this particular study, the immunoblotting method used to measure CagA antibodies was less sensitive than EIA-serology in detecting an ongoing H. pylori infection. In the present study, all except three patients had a positive CagA band on the immunoblot, including all EIA-serology positive patients. We have studied the sensitivity and specificity of this particular immunoblotting method previously, with good results. However, not even the immunoblotting method used in our present study can rule out a previous H. pylori infection with 100% certainty, as all H. pylori strains are not CagA positive. On the other hand, the common occurrence of H. pylori antibodies in patients with autoimmune type of atrophic gastritis could be a random effect, as the H. pylori infection rate has been nearly 100% in populations now presenting as the peak age group of autoimmune gastritis. This could also be one explanation why H. pylori prevalence studied by immunoblotting in patients with serological markers of autoimmune type gastritis (PCA and IF antibodies) was no different from patients with no such markers in our study.
Thus, it still remains to be shown if H. pylori infection is crucial for the development of autoimmune type atrophic gastritis. However, bacterial infections might be important in autoimmune processes, as recently suggested by Torchinsky et al. In this in vitro study, phagocytosis of immune cells infected with bacteria and undergoing apoptosis promoted Th17 cell differentiation, the cell type having a potential role in autoimmunity. Thus, it is tempting to speculate that cells in the gastric mucosa infected with H. pylori could trigger an autoimmune response.
In conclusion, atrophic corpus gastritis, including autoimmune type severe atrophy with vitamin B12 malabsorption, is associated with a longstanding H. pylori infection in most cases. There is an urgent need for population-based studies to assess the effect of H. pylori eradication on the development of vitamin B12 malabsorption.
Our deepest appreciation goes to the late Pirjo Kosunen for her skilful and assiduous assistance. We also thank Biohit PLC.Diagnostics for providing laboratory tests for pepsinogens and gastrin-17.
Autoimmune type atrophic gastritis is a severe gastric atrophy associated with pernicious anaemia with lifelong substitution therapy with vitamin B12. Longstanding Helicobacter pylori (H. pylori) infection proceeds in about 50% of patients to atrophic gastritis. H. pylori infection is much more prevalent than autoimmune type gastritis, and the association of these two conditions is possible without a causal relationship.
Previous studies have shown that H. pylori shares several epitopes with the proton pump, and the b-subunit of this pump is the causative antigen in autoimmune gastritis. In animal models, the passive transfer of these antibodies does not cause disease, but CD4+ T-cells are responsible for the gastritis. Recently, it has been shown that bacterial infection can modify the immune response in the direction seen in autoimmune diseases, i.e. Th17 cell differentiation, thus linking infection and autoimmunity.
Innovations and breakthroughs
It is difficult to differentiate severe end stage H. pylori atrophic gastritis and autoimmune type gastric atrophy, because the autoimmune serum markers appear in H. pylori gastritis with increasing grade of atrophy, as shown in previous studies and confirmed in our study. The preatrophic stage of autoimmune type gastritis without H. pylori infection is an unknown entity. Several patients with autoimmune type gastric atrophy have signs of a previous H. pylori infection when studied with sensitive methods and remain positive for years, as shown in this study.
If H. pylori initiates the apoptosis that leads to gastric atrophy and vitamin B12 deficiency, eradication of the bacteria before the development of severe atrophic changes should abolish the development of pernicious anaemia and the need of lifelong vitamin B12 substitution therapy.
This is a very interesting paper and asks quite an important question as to whether there is an association between H. pylori infection and autoimmune type atrophic gastritis. This work could be accepted after revision.
3 Andrès E, Loukili NH, Noel E, Kaltenbach G, Abdelgheni MB, Perrin AE, Noblet-Dick M, Maloisel F, Schlienger JL, Blicklé JF. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ 2004; 171: 251-259 PubMed DOI
4 Karlsson FA, Burman P, Lööf L, Mårdh S. Major parietal cell antigen in autoimmune gastritis with pernicious anemia is the acid-producing H+,K+-adenosine triphosphatase of the stomach. J Clin Invest 1988; 81: 475-479 PubMed DOI
6 Valle J, Kekki M, Sipponen P, Ihamäki T, Siurala M. Long-term course and consequences of Helicobacter pylori gastritis. Results of a 32-year follow-up study. Scand J Gastroenterol 1996; 31: 546-550 PubMed DOI
7 Claeys D, Faller G, Appelmelk BJ, Negrini R, Kirchner T. The gastric H+,K+-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy. Gastroenterology 1998; 115: 340-347 PubMed DOI
8 D'Elios MM, Amedei A, Azzurri A, Benagiano M, Del Prete G, Bergman MP, Vandenbroucke-Grauls CM, Appelmelk BJ. Molecular specificity and functional properties of autoreactive T-cell response in human gastric autoimmunity. Int Rev Immunol 2005; 24: 111-122 PubMed DOI
9 Bergman MP, Vandenbroucke-Grauls CM, Appelmelk BJ, D'Elios MM, Amedei A, Azzurri A, Benagiano M, Del Prete G. The story so far: Helicobacter pylori and gastric autoimmunity. Int Rev Immunol 2005; 24: 63-91 PubMed DOI
11 Suter PM, Golner BB, Goldin BR, Morrow FD, Russell RM. Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis. Gastroenterology 1991; 101: 1039-1045 PubMed
12 Lahner E, Bordi C, Cattaruzza MS, Iannoni C, Milione M, Delle Fave G, Annibale B. Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection. Aliment Pharmacol Ther 2005; 22: 471-481 PubMed DOI
13 Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007; 56: 772-781 PubMed DOI
14 Marino MC, de Oliveira CA, Rocha AM, Rocha GA, Clementino NC, Antunes LF, Oliveira RA, Martins AS, Del Puerto HL, D'Almeida V, Galdieri L, Pedroso ER, Cabral MM, Nogueira AM, Queiroz DM. Long-term effect of Helicobacter pylori eradication on plasma homocysteine in elderly patients with cobalamin deficiency. Gut 2007; 56: 469-474 PubMed DOI
15 Oksanen A, Veijola L, Korudanova B, Sipponen P, Sarna S, Rautelin H. Role of earlier gastroscopy in predicting findings on repeat gastroscopy in a population with a low H. pylori prevalence. Scand J Gastroenterol 2008; 43: 1044-1049 PubMed DOI
16 Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996; 20: 1161-1181 PubMed DOI
17 Oksanen A, Veijola L, Sipponen P, Schauman KO, Rautelin H. Evaluation of Pyloriset Screen, a rapid whole-blood diagnostic test for Helicobacter pylori infection. J Clin Microbiol 1998; 36: 955-957 PubMed
18 Kokkola A, Rautelin H, Puolakkainen P, Sipponen P, Färkkilä M, Haapiainen R, Kosunen TU. Diagnosis of Helicobacter pylori infection in patients with atrophic gastritis: comparison of histology, 13C-urea breath test, and serology. Scand J Gastroenterol 2000; 35: 138-141 PubMed DOI
19 Feldman RA, Deeks JJ, Evans SJ. Multi-laboratory comparison of eight commercially available Helicobacter pylori serology kits. Helicobacter pylori Serology Study Group. Eur J Clin Microbiol Infect Dis 1995; 14: 428-433 PubMed DOI
20 Kokkola A, Kosunen TU, Puolakkainen P, Sipponen P, Harkonen M, Laxen F, Virtamo J, Haapiainen R, Rautelin H. Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis. APMIS 2003; 111: 619-624 PubMed DOI
21 Veijola L, Oksanen A, Linnala A, Sipponen P, Rautelin H. Persisting chronic gastritis and elevated Helicobacter pylori antibodies after successful eradication therapy. Helicobacter 2007; 12: 605-608 PubMed DOI
22 Ye W, Held M, Enroth H, Kraaz W, Engstrand L, Nyrén O. Histology and culture results among subjects with antibodies to CagA but no evidence of Helicobacter pylori infection with IgG ELISA. Scand J Gastroenterol 2005; 40: 312-318 PubMed DOI
23 Veijola L, Oksanen A, Sipponen P, Rautelin H. Evaluation of a commercial immunoblot, Helicoblot 2.1, for diagnosis of Helicobacter pylori infection. Clin Vaccine Immunol 2008; 15: 1705-1710 PubMed DOI
24 Oksanen A, Sipponen P, Karttunen R, Miettinen A, Veijola L, Sarna S, Rautelin H. Atrophic gastritis and Helicobacter pylori infection in outpatients referred for gastroscopy. Gut 2000; 46: 460-463 PubMed DOI
25 Annibale B, Lahner E, Santucci A, Vaira D, Pasquali A, Severi C, Mini R, Figura N, Delle Fave G. CagA and VacA are immunoblot markers of past Helicobacter pylori infection in atrophic body gastritis. Helicobacter 2007; 12: 23-30 PubMed DOI
26 Simán JH, Engstrand L, Berglund G, Florén CH, Forsgren A. Evaluation of western blot CagA seropositivity in Helicobacter pylori-seropositive and -seronegative subjects. Clin Diagn Lab Immunol 2005; 12: 304-309 PubMed DOI
27 Storskrubb T, Aro P, Ronkainen J, Vieth M, Stolte M, Wreiber K, Engstrand L, Nyhlin H, Bolling-Sternevald E, Talley NJ, Agréus L. A negative Helicobacter pylori serology test is more reliable for exclusion of premalignant gastric conditions than a negative test for current H. pylori infection: a report on histology and H. pylori detection in the general adult population. Scand J Gastroenterol 2005; 40: 302-311 PubMed DOI
30 Segni M, Borrelli O, Pucarelli I, Delle Fave G, Pasquino AM, Annibale B. Early manifestations of gastric autoimmunity in patients with juvenile autoimmune thyroid diseases. J Clin Endocrinol Metab 2004; 89: 4944-4948 PubMed DOI
31 Sorrentino D, Faller G, DeVita S, Avellini C, Labombarda A, Ferraccioli G, Kahlow-Toussaint S. Helicobacter pylori associated antigastric autoantibodies: role in Sjögren's syndrome gastritis. Helicobacter 2004; 9: 46-53 PubMed DOI
32 Annibale B, Negrini R, Caruana P, Lahner E, Grossi C, Bordi C, Delle Fave G. Two-thirds of atrophic body gastritis patients have evidence of Helicobacter pylori infection. Helicobacter 2001; 6: 225-233 PubMed DOI
33 Annibale B, Lahner E, Negrini R, Baccini F, Bordi C, Monarca B, Delle Fave G. Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis. World J Gastroenterol 2005; 11: 5351-5357 PubMed
34 Mini R, Annibale B, Lahner E, Bernardini G, Figura N, Santucci A. Western blotting of total lysate of Helicobacter pylori in cases of atrophic body gastritis. Clin Chem 2006; 52: 220-226 PubMed DOI
S- Editor Wang JL L- Editor Stewart GJ E- Editor Zheng XM