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Discovery Medicine 2022Pernicious anemia (PA) is an autoimmune disease characterized by cobalamin deficiency (CD) due to immune-mediated chronic atrophic gastritis (CAG). CD results from poor...
Pernicious anemia (PA) is an autoimmune disease characterized by cobalamin deficiency (CD) due to immune-mediated chronic atrophic gastritis (CAG). CD results from poor absorption of dietary cobalamin from the terminal ileum, triggered by positive intrinsic factor (IF) antibodies. It is the most common cause of CD worldwide. Despite advances in understanding biochemistry and pathogenesis of PA, its diagnosis can be extremely challenging as the disease may present with hematological as well as nonhematological manifestations and also because of unreliable serum cobalamin assays. Nonhematological manifestations may present in a patient with PA even in the absence of hematological findings. Herein, an overview of common and uncommon nonhematological manifestations of PA is discussed.
Topics: Humans; Anemia, Pernicious
PubMed: 36476278
DOI: No ID Found -
Translational Research : the Journal of... Oct 2022Gender-sex differences in autoimmune diseases are gaining increasing attention due to their effects on prevalence and clinical features. Data on gender-sex differences...
Gender-sex differences in autoimmune diseases are gaining increasing attention due to their effects on prevalence and clinical features. Data on gender-sex differences in autoimmune atrophic gastritis (AAG), a chronic not-self-limiting inflammatory condition characterized by corpus-oxyntic mucosa atrophy sparing the antrum, are lacking. This study aimed to assess possible gender-sex differences of clinical, serological, histological, and genetic features in AAG patients. Cross-sectional study on 435 patients with histological-AAG, stratified according to female-male gender. In subsets of patients, serum gastric-autoantibodies against intrinsic-factor (IFA) and parietal-cells (PCA) by luminescent-immunoprecipitation-system (LIPS) (n = 81) and of HLA-DRB1-genotyping (n = 89) were available and stratified according to sex. Female AAG-patients were preponderant: 69.2%vs30.8%, P < 0.0001(ratio 2.2:1). Females were more frequently PCA and/or IFA-positive than males (90.9%vs73.1%, P = 0.0361). HLA-DRB1*06-alleles were significantly more frequent in females [30%vs4%, P = 0.01, OR 10.1(95%CI 1.3-80.4); HLA-DRB1*04-alleles were more frequent and HLA-DRB1*03 and *05-alleles less frequent in females without reaching statistical significance. At logistic regression, iron-deficiency-anemia [OR 3.6(95%CI 1.9-7.0)], body-mass-index <25m/kg [OR 3.1(95%CI 1.7-5.6)], autoimmune-thyroid-disease [OR 2.5(95%CI 1.4-4.5), and dyspepsia [OR 2.4(95%CI 1.4-4.3) were significantly associated to females. Body-mass-index>25m/kg [OR 3.2(95%CI1.8-5.6)], absence of autoimmune-thyroid-disease [OR 2.3(95%CI 1.3-4.2)] and dyspepsia [OR 2.1(95%CI 1.2-3.7)], smoking habit [OR 1.8(95%CI 1.1-3.1)], and pernicious-anemia [OR 1.7(95%CI 1.0-3.0)], were significantly associated to males. AAG was preponderant in women who showed stronger autoimmune serological responsiveness and different HLA-DRB1 association. AAG showed differential clinical profiles in female and male patients occurring mainly in normal weight, dyspeptic women with iron-deficiency anemia and autoimmune thyroid disease, but in overweight male smokers with pernicious anemia. Stratification for sex and gender should be considered in future genetic, immunological, and clinical studies on autoimmune atrophic gastritis.
Topics: Anemia; Atrophy; Autoantibodies; Autoimmune Diseases; Cross-Sectional Studies; Dyspepsia; Female; Gastritis, Atrophic; HLA-DRB1 Chains; Humans; Male; Sex Characteristics
PubMed: 35470008
DOI: 10.1016/j.trsl.2022.04.006 -
The New England Journal of Medicine Oct 2019
Topics: Anemia, Pernicious; Atrophy; Glossitis; Humans; Male; Middle Aged; Tongue
PubMed: 31618542
DOI: 10.1056/NEJMicm1902490 -
Clinical Chemistry Oct 2023Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and... (Review)
Review
BACKGROUND
Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important.
CONTENT
The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods.
SUMMARY
Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications.
Topics: Humans; Gastritis, Atrophic; Gastrins; Intrinsic Factor; Reproducibility of Results; Atrophy; Biomarkers; Helicobacter pylori
PubMed: 37680186
DOI: 10.1093/clinchem/hvad082 -
BMC Cancer May 2024Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly...
BACKGROUND
Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly contradictory. The purpose of this study was to investigate the potential causal relationship between PA and cancers through bidirectional two-sample Mendelian randomized (MR) analysis.
METHODS
The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests.
RESULTS
Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P < 0.05). After Benjamini-Hochberg correction test, there was still a causal correlation between PA and gastric or prostate cancer (P' < 0.05), while there was only an implied causal association between PA and testicular cancer and malignant melanoma of skin (P'> 0.05). There was still a reverse causal relationship between gastric cancer and PA (P'< 0.05), while prostate cancer shows an implied reverse causal relationship(P'> 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy.
CONCLUSIONS
PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.
Topics: Humans; Mendelian Randomization Analysis; Anemia, Pernicious; Male; Stomach Neoplasms; Neoplasms; Testicular Neoplasms; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Female
PubMed: 38741062
DOI: 10.1186/s12885-024-12354-y -
The American Journal of Gastroenterology Dec 2023Corpus-restricted atrophic gastritis is a chronic inflammatory disorder leading to possible development of type 1 neuroendocrine tumors (T1gNET), intraepithelial...
INTRODUCTION
Corpus-restricted atrophic gastritis is a chronic inflammatory disorder leading to possible development of type 1 neuroendocrine tumors (T1gNET), intraepithelial neoplasia (IEN), and gastric cancer (GC). We aimed to assess occurrence and predictors of gastric neoplastic lesions in patients with corpus-restricted atrophic gastritis at long-term follow-up.
METHODS
A prospective single-center cohort of patients with corpus-restricted atrophic gastritis adhering to endoscopic-histological surveillance was considered. Follow-up gastroscopies were scheduled according to the management of epithelial precancerous conditions and lesions of the stomach guidelines. In case of new/worsening of known symptoms, gastroscopy was anticipated. Cox regression analyses and Kaplan-Meier survival curves were obtained.
RESULTS
Two hundred seventy-five patients with corpus-restricted atrophic gastritis (72.0% female, median age 61 [23-84] years) were included. At a median follow-up of 5 (1-17) years, the annual incidence rate person-year was 0.5%, 0.6%, 2.8%, and 3.9% for GC/high-grade IEN, low-grade IEN, T1gNET, and all gastric neoplastic lesions, respectively. All patients showed at baseline operative link for gastritis assessment (OLGA)-2, except 2 low-grade (LG) IEN patients and 1 T1gNET patient with OLGA-1. Age older than 60 years (hazard ratio [HR] 4.7), intestinal metaplasia without pseudopyloric metaplasia (HR 4.3), and pernicious anemia (HR 4.3) were associated with higher risk for GC/HG-IEN or LG-IEN development and shorter mean survival time for progression (13.4, 13.2, and 11.1, respectively, vs 14.7 years, P = 0.01). Pernicious anemia was an independent risk factor for T1gNET (HR 2.2) and associated with a shorter mean survival time for progression (11.7 vs 13.6 years, P = 0.04) as well as severe corpus atrophy (12.8 vs 13.6 years, P = 0.03).
DISCUSSION
Patients with corpus-restricted atrophic gastritis are at increased risk for GC and T1gNET despite low-risk OLGA scores, and those aged older than 60 years with corpus intestinal metaplasia or pernicious anemia seem to display a high-risk scenario.
Topics: Humans; Female; Aged; Middle Aged; Male; Gastritis, Atrophic; Incidence; Cohort Studies; Anemia, Pernicious; Prospective Studies; Gastritis; Risk Factors; Stomach Neoplasms; Precancerous Conditions; Metaplasia; Helicobacter Infections; Gastric Mucosa
PubMed: 37207305
DOI: 10.14309/ajg.0000000000002327 -
World Journal of Gastroenterology Nov 2023As an emerging potential risk factor for gastric cancer, autoimmune gastritis (AIG) has garnered increasing attention from researchers.
BACKGROUND
As an emerging potential risk factor for gastric cancer, autoimmune gastritis (AIG) has garnered increasing attention from researchers.
AIM
To analyze the research overview and popular topics in the field of AIG using bibliometrics.
METHODS
Relevant publications on AIG in the Web of Science Core Collection were collated, and data visualization and analysis of the number of publications, countries, institutions, journals, authors, keywords, and citations were performed using software such as VOSviewer, CiteSpace, and Scimago Graphic.
RESULTS
In total, 316 relevant articles were included in the analysis. From 2015 to 2022, the number of publications increased annually. The countries, institutions, authors, and journals with the highest number of publications in this field were Italy, Monash University, Toh BH, and Internal Medicine. The main keywords used in this field of research were pathogenesis, , autoantibody, parietal cell antibody, atrophic gastritis, classification, diagnosis, autoimmune disease, risk, cancer, gastric cancer, vitamin B12 deficiency, and pernicious anemia. The following directions may be popular for future research: (1) The role of in the pathogenesis of AIG; (2) diagnostic criteria for AIG and reference values for serum antibodies; (3) comorbidity mechanisms between AIG and other autoimmune diseases; (4) specific risks of AIG complicating gastric and other cancers; and (5) the role of vitamin B12 supplementation in patients with early-stage AIG.
CONCLUSION
This bibliometric analysis reported on popular topics and emerging trends in AIG, with diagnosis and prognosis being research hotspots in this field.
Topics: Humans; Autoantibodies; Autoimmune Diseases; Bibliometrics; Gastritis; Gastritis, Atrophic; Stomach Neoplasms
PubMed: 38075850
DOI: 10.3748/wjg.v29.i42.5781 -
Deutsche Medizinische Wochenschrift... Apr 2022Autoimmune gastritis (AIG) is a chronic immune-mediated inflammation of the gastric corpus/fundus mucosa leading to progressive atrophy of the oxyntic gastric glands... (Review)
Review
Autoimmune gastritis (AIG) is a chronic immune-mediated inflammation of the gastric corpus/fundus mucosa leading to progressive atrophy of the oxyntic gastric glands (AOM) and their consecutive loss of function. Possible clinical consequences of AIG include iron deficiency anemia, pernicious anemia, gastric neuroendocrine tumors (gNET), and gastric adenocarcinoma. This article provides a review of interdisciplinary aspects of the diagnosis and treatment of AIG.
Topics: Anemia, Iron-Deficiency; Autoimmune Diseases; Gastric Mucosa; Gastritis; Humans; Stomach Neoplasms
PubMed: 35405749
DOI: 10.1055/a-1520-3562 -
Clinica Chimica Acta; International... Mar 2024The challenges in the management of human diseases are largely determined by the precision, speed and ease of diagnostic procedures available. Developments in biomedical... (Review)
Review
The challenges in the management of human diseases are largely determined by the precision, speed and ease of diagnostic procedures available. Developments in biomedical engineering technologies have greatly helped in transforming human health care, especially for disease diagnosis which in turn lead to better patient outcomes. One such development is in the form of microfluidic chip technology which has transformed various aspects of human health care. We present in this review, a comprehensive account on the utility of microfluidic chip technologies for the diagnosis of autoimmune disorders, cardiovascular diseases (CVDs), infectious diseases, and neurodegenerative conditions. We have included the diseases posing global threat such as rheumatoid arthritis, diabetes, pernicious anemia, tuberculosis, COVID-19, influenza, alzheimer's, multiple sclerosis, and epilepsy. Apart from discussing the ways of microfluidic chip in diagnosis, we included a section presenting electrochemical, electrical, optical, and acoustic detection technologies for the precise diagnosis of CVDs. Microfluidics platforms have thus revolutionized novel capabilities in addressing the requirements of point-of-care diagnostics enabling miniaturization by integrating multiple laboratory functions into a single chip resulting in "one flow - one solution" systems. Hence, the precision and early diagnoses of diseases are now possible due to the advancements of microfluidics-based technology.
Topics: Humans; Microfluidics; Communicable Diseases; Electricity; Lab-On-A-Chip Devices; Microfluidic Analytical Techniques
PubMed: 38395126
DOI: 10.1016/j.cca.2024.117841 -
Frontiers in Genetics 2022Expanded tandem repeat DNAs are associated with various unusual chromosomal lesions, despiralizations, multi-branched inter-chromosomal associations, and fragile sites.... (Review)
Review
Expanded tandem repeat DNAs are associated with various unusual chromosomal lesions, despiralizations, multi-branched inter-chromosomal associations, and fragile sites. Fragile sites cytogenetically manifest as localized gaps or discontinuities in chromosome structure and are an important genetic, biological, and health-related phenomena. Common fragile sites (∼230), present in most individuals, are induced by aphidicolin and can be associated with cancer; of the 27 molecularly-mapped common sites, none are associated with a particular DNA sequence motif. Rare fragile sites ( 40 known), 5% of the population (may be as few as a single individual), can be associated with neurodevelopmental disease. All 10 molecularly-mapped folate-sensitive fragile sites, the largest category of rare fragile sites, are caused by gene-specific CGG/CCG tandem repeat expansions that are aberrantly CpG methylated and include FRAXA, FRAXE, FRAXF, FRA2A, FRA7A, FRA10A, FRA11A, FRA11B, FRA12A, and FRA16A. The minisatellite-associated rare fragile sites, FRA10B, FRA16B, can be induced by AT-rich DNA-ligands or nucleotide analogs. Despiralized lesions and multi-branched inter-chromosomal associations at the heterochromatic satellite repeats of chromosomes 1, 9, 16 are inducible by de-methylating agents like 5-azadeoxycytidine and can spontaneously arise in patients with ICF syndrome (mmunodeficiency entromeric instability and acial anomalies) with mutations in genes regulating DNA methylation. ICF individuals have hypomethylated satellites I-III, alpha-satellites, and subtelomeric repeats. Ribosomal repeats and subtelomeric D4Z4 megasatellites/macrosatellites, are associated with chromosome location, fragility, and disease. Telomere repeats can also assume fragile sites. Dietary deficiencies of folate or vitamin B12, or drug insults are associated with megaloblastic and/or pernicious anemia, that display chromosomes with fragile sites. The recent discovery of many new tandem repeat expansion loci, with varied repeat motifs, where motif lengths can range from mono-nucleotides to megabase units, could be the molecular cause of new fragile sites, or other chromosomal lesions. This review focuses on repeat-associated fragility, covering their induction, cytogenetics, epigenetics, cell type specificity, genetic instability (repeat instability, micronuclei, deletions/rearrangements, and sister chromatid exchange), unusual heritability, disease association, and penetrance. Understanding tandem repeat-associated chromosomal fragile sites provides insight to chromosome structure, genome packaging, genetic instability, and disease.
PubMed: 36468036
DOI: 10.3389/fgene.2022.985975