intrinsic-factor and Helicobacter-Infections

Pernicious anemia (PA) is a complex, autoimmune, multi-factorial disease. Rapid progress has been made in the understanding of susceptibility to a spectrum of other autoimmune diseases through genome wide association studies (GWAS). However, PA has been conspicuous by its absence from this work. Here, we examine the evidence that PA has a significant heritable component through epidemiological evidence and its co-occurrence with other autoimmune diseases. Further, we consider how knowledge of the genetic susceptibility to other autoimmune diseases may provide insight into the etiology of PA.

Topics: Anemia, Pernicious; Cobamides; Comorbidity; Genetic Predisposition to Disease; Genome-Wide Association Study; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Polymorphism, Genetic

Gastric exocrine secretion, both acid and non-acid, is required for micronutrients absorption, such as iron, calcium and vitamin B12, drugs absorption, protein digestion. Clinical presentation of a gastric secretion impairment might be then characterized by the presence of both gastrointestinal and non-gastrointestinal specific symptoms (i.e. anemia) or to a non-response to therapies. The main factor that impairs gastric exocrine secretion homeostasis is mucosal chronic inflammation that principally occurs after colonization by Helicobacter pylori (Hp). The extent and distribution of gastritis ultimately determine the clinical outcome linked to differences in gastric acid secretion status, the involvement of gastric body leading to a decrease in gastric exocrine secretion with possible progression to mucosal atrophy towards cancer. A correct clinical strategy in the management of Hp infected patients should be then to early identify body involvement, a diagnosis generally missed in that body biopsies are not routinely performed. The use of gastric serological markers, gastrin and pepsinogens, are helpful in suspecting the presence of mucosal atrophy but their diagnostic accuracy for non-atrophic chronic gastritis topography is not adequate despite a good specificity due to the low sensitivity, of all the available biomarkers. Gastric serology associated to anemia/iron-deficiency screening might nevertheless been helpful in the framing of patients that undergo endoscopy in order to highlight the need of extensive mucosal biopsies sampling.

Topics: Absorption; Anemia; Biomarkers; Biopsy; Gastric Acid; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Micronutrients; Models, Biological; Parietal Cells, Gastric; Pepsinogens; Secretory Rate; Stomach

Patients of chronic gastritis should be investigated with gastric mucosal biopsy, parietal cell antibody, intrinsic factor antibody, Helicobacter pylori antibody, urea breath test or faecal antigen test for Helicobacter pylori, to accurately classify them. The results of these tests will indicate Helicobacter pylori infection (present or past), the role of hereditary factor (intrinsic factor antibody present or absent) and the success or failure of Helicobacter pylori eradication treatment.

Topics: Biopsy; Chronic Disease; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Parietal Cells, Gastric

Topics: Animals; Autoantibodies; Diagnosis, Differential; Gastritis, Atrophic; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Humans; Intrinsic Factor; Parietal Cells, Gastric; Prognosis; Vitamin B 12

Several genome-wide association studies (GWAS) have identified a strong association between serum vitamin B12 and fucosyltransferase 2 (FUT2), a gene associated with susceptibility to Helicobacter pylori infection. Hazra et al. conducted a meta-analysis of three GWAS and found three additional loci in MUT, CUBN and TCN1. Other GWAS conducted in Italy and China confirmed the association for FUT2 gene. Alpha-2-fucosyltransferase (FUT2) catalyzes fucose addition to form H-type antigens in exocrine secretions. FUT2 non-secretor variant produces no secretion of H-type antigens and is associated with high-plasma vitamin B12 levels. This association was explained by the influence of FUT2 on H. pylori, which is a risk factor of gastritis, a main cause of vitamin B12 impaired absorption. However, we recently showed that H. pylori serology had no influence on FUT2 association with vitamin B12, in a large sample population, suggesting the involvement of an alternative mechanism. GIF is another gene associated with plasma levels of vitamin B12 and gastric intrinsic factor (GIF) is a fucosylated protein needed for B12 absorption. Inherited GIF deficiency produces B12 deficiency unrelated with gastritis. We report 2 families with heterozygous GIF mutation, 290T>C, M97T, with decreased binding affinity of GIF for vitamin B12 and one family with heterozygous GIF mutation 435_437delGAA, K145_N146delinsN and no B12 binding activity of mutated GIF. All cases with vitamin B12 deficit carried the FUT2 rs601338 secretor variant. Ulex europeus binding to GIF was influenced by FUT2 genotypes and GIF concentration was lower, in gastric juice from control subjects with the secretor genotype. GIF290C allele was reported in 5 European cases and no Africans among 1282 ambulatory subjects and was associated with low plasma vitamin B12 and anaemia in the single case bearing the FUT2 secretor variant. We concluded that FUT2 secretor variant worsens B12 status in cases with heterozygous GIF mutations by impairing GIF secretion, independently from H. pylori-related gastritis.

Topics: Adult; Anemia, Pernicious; Female; Fucosyltransferases; Galactoside 2-alpha-L-fucosyltransferase; Genome-Wide Association Study; Helicobacter Infections; Heterozygote; Humans; Intrinsic Factor; Male; Mutation; Vitamin B 12; Young Adult

To assess the predictive value for chronic autoimmune gastritis (AIG) of the combined assay of anti-parietal-cell antibodies (PCA), anti-intrinsic-factor antibodies (IFA), anti-Helicobacter pylori (Hp) antibodies, and measurement of blood gastrin.. We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency.. 83 patients (45.8%) tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1) 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2) 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3) 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4) 21 patients with multifocal atrophic gastritis with "borderline" PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases.. The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic "serological biopsy."

Topics: Aged; Antibodies; Autoimmune Diseases; Biopsy; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Lymphocytes; Male; Middle Aged; Parietal Cells, Gastric; Serologic Tests

To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis.. 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.. 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.. 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.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Biomarkers; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoblotting; Immunoenzyme Techniques; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Pepsinogen C; Risk Factors; Severity of Illness Index; Vitamin B 12 Deficiency

Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases.. To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients.. Sixty-two H pylori-positive elderly patients with cobalamin deficiency were prospectively studied.. Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication.. Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) micromol/l at the 6 month follow-up (p<0.001) and to 13.1 (3.8) micromol/l 12 months after H pylori eradication (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p<0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p<0.001) months after treatment.. The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.

Topics: Aged; Aged, 80 and over; Autoantibodies; Female; Follow-Up Studies; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Homocysteine; Humans; Intrinsic Factor; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Prospective Studies; Vitamin B 12 Deficiency

To determine whether serum vitamin B12 levels in non-vitamin B12 deficient healthy adults correlate with serological evidence of H. pylori infection.. An association between H. pylori infection and vitamin B12 deficiency has been recently reported.. 133 adults, presenting to a community based primary care clinic who met the following exclusion criteria; history of H. pylori eradication or antacid use, liver disease, inflammatory bowel disease, previous gastrointestinal surgery, a vegetarian diet or multivitamin supplementation were studied. Blood was drawn for a complete blood count, serum vitamin B12, gastrin, folic acid and H. pylori IgG antibodies. Subjects with vitamin B12 < or = 145 ng/mL (deficient range) were excluded.. Of 133 subjects 96 (72.2%) were seropositive for H. pylori IgG antibodies (HP+). Age of HP(+) subjects did not differ from that of seronegative subjects (HP-); 52.8 +/- 1.6 mean +/- SE versus 49.2 +/- 2.9 ( = NS). Prevalence of HP seropositivity was significantly higher among subjects with borderline (>145-180 pg/mL) or low normal (>180-250 pg/mL) vitamin B12 levels than among those with vitamin B12 > 250 pg/mL; among 25 subjects with vitamin B12 > 145-180 pg/mL 92% were seropositive and among 47 subjects with vitamin B12 > 180-250 pg/mL 89% were seropositive as compared with 31/61 (51%) of subjects with B12 > 250 pg/mL, Fisher exact test < 0.0001. Vitamin B12 levels did not correlate with age (r = -0.07). Gastrin levels (pg/mL) did not differ significantly between groups; 70.2 +/- 5.8 in HP(+) versus 56.0 +/- 12.4 in HP(-).. The higher prevalence of H. pylori infection among subjects with serum vitamin B12 levels that are within the lower end of the normal range suggests a causal relationship between H pylori infection and vitamin B12 levels in healthy adults.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Erythrocyte Indices; Female; Folic Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Hematocrit; Hemoglobins; Humans; Immunoglobulin G; Intrinsic Factor; Male; Middle Aged; Parietal Cells, Gastric; Prevalence; Reference Values; Seroepidemiologic Studies; Statistics as Topic; Vitamin B 12

Intrinsic factor is produced primarily by chief cells in rat and mouse, but 4 to 11% of isolated rat parietal cells also contain intrinsic factor. To test whether local conditions could alter the distribution of intrinsic factor expression, two rodent models of chronic lymphocytic gastric inflammation were examined. Immunocytochemistry was performed using antiserum against human intrinsic factor and H/K ATPase (a parietal cell marker), counting the percent of intrinsic factor-positive parietal cells. HLA-B27 transgenic rats develop chronic gastritis at age 3 months. Congenic controls expressed intrinsic factor in 8.9 +/- 3.8% (mean +/- SD) of parietal cells; in inflamed areas of transgenic rats 21 +/- 5.2% (P < 0.0001) of parietal cells were positive. In adjacent areas without inflammatory infiltrate 16 +/- 3.6% of parietal cells contained intrinsic factor. C57BL/6 mice inoculated with Helicobacter felis develop gastritis by 4 weeks. After 4 and 8 weeks of infection, intrinsic factor-positive parietal cells increased from 7.8 +/- 2.8% in the congenic controls to 17.6 +/- 4.1% in the inflamed gastric body (P < 0.0001). Isolated rat parietal cells incubated with interleukin-1beta demonstrated a twofold increase in intrinsic factor-positive parietal cells. These studies are consistent with the concept that intrinsic factor expression is both predetermined in chief cells and can be expressed in parietal cells in response to local inflammatory factors. The differences between inflamed and adjacent noninflamed areas in the rat model suggest a tissue gradient of soluble inducer(s), possibly cytokines.

Topics: Animals; Animals, Genetically Modified; Cell Line; Cell Separation; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; HLA-B27 Antigen; Immunohistochemistry; Interleukin-1; Intrinsic Factor; Mice; Mice, Inbred C57BL; Parietal Cells, Gastric; Rats; Rats, Inbred Lew

To assess the effect of increasing age on circulating gastrin, we surveyed serum gastrin, Helicobactor pylori seroantibody status and gastric autoimmunity in 366 hospitalized patients aged 15-90 years. Data were subjected to multivariate analysis, using logarithmic transformation to normalize the distribution of gastrin concentrations (presented as geometric means and 95% CIs). The frequency of H. pylori-positive antibody status increased with age from 28% in the second decade to > 70% beyond the fourth decade. Fasting gastrin concentrations rose significantly from 44 ng/l (41-48) in the second decade to 95 ng/l (67-131) by the eighth decade (p = 0.001) in the total group. Twenty-seven patients (6.8% of the total) tested positive for gastric auto-antibodies: 2% of patients in the second decade, rising to 15.9% in the eighth decade. These patients formed a distinct group with respect to circulating gastrin concentrations. Excluding these 27, fasting gastrin concentrations still rose significantly, from 44 ng/l (41-48) in the second decade, to 67 ng/l (50-89) in the eighth decade (p = 0.003) in the remaining 341 patients. Fasting gastrin concentrations were significantly higher in patients who were H. pylori-seropositive (59 ng/l, 54-64 vs. sero-negative 41 ng/l, 37-46) (p = 0.002), and there was no increase in circulating gastrin concentrations with increasing age in either the H. pylori-positive or the H. pylori-negative group. The increase in circulating fasting gastrin observed with increasing age is due to an increased incidence of gastric antibodies associated with auto-immune atrophic gastritis, and an increased incidence of H. pylori infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Anemia, Pernicious; Antibodies, Bacterial; Autoantibodies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Intrinsic Factor; Middle Aged; Multivariate Analysis; Parietal Cells, Gastric