Home High frequency of anti-parietal cell antibody (APCA) and intrinsic factor blocking antibody (IFBA) in individuals with severe vitamin B12 deficiency – an observational study in primary care patients
Article
Licensed
Unlicensed Requires Authentication

High frequency of anti-parietal cell antibody (APCA) and intrinsic factor blocking antibody (IFBA) in individuals with severe vitamin B12 deficiency – an observational study in primary care patients

  • Maria Salinas EMAIL logo , Emilio Flores , Maite López-Garrigós and Carlos Leiva-Salinas
Published/Copyright: November 12, 2019
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 58 Issue 3

Abstract

Background

Vitamin B12 deficiency is common worldwide and is also linked to several diseases including autoimmune atrophic gastritis (AAG). The presence of anti-parietal cell antibodies (APCA) and/or intrinsic factor blocking antibodies (IFBA) is indicative of AAG that may develop into pernicious anemia. Both conditions are known to be associated with an increased risk of gastric carcinoma. The aim of this study was to estimate the frequency of individuals positive for APCA and IFBA antibodies in primary care patients with severe vitamin B12 deficiency.

Methods

An observational study was designed and 5468 consecutive patients from primary care with a request for vitamin B12 status were included and add-on testing for APCA and IFBA that were automatically registered if severe vitamin B12 deficiency was identified (<73.8 pmol/L). For patients included in the intervention, study demographic data, mean corpuscular volume (MCV) and hemoglobin values were collected.

Results

Seventy-seven patients with severe vitamin B12 deficiency were identified and out of these 44 (57%) presented with antibodies to APCA and 11 (14%) to IFBA, 25 (32.5%) had anemia, and 25 (32.5%) had macrocytosis. The majority of APCA and/or IFBA positive patients were found in the age group >70 years. Both anemia and macrocytosis were more common among APCA positive patients but the association was not statistically significant, neither was the correlation between IFBA status and anemia and/or macrocytosis. Among the patients with anemia, 10 (39%) had macrocytosis, although the rate of macrocytosis among patients with or without anemia did not differ significantly.

Conclusions

The automated analysis strategy of measuring antibodies to APCA and IFBA in patients with severe vitamin B12 deficiency, efficiently detected positivity in more than 60% the patients. The result point to the presence of a high rate of otherwise undetected AAG and the potential clinical utility of APCA and IFBA as markers in primary care.

Keywords: clinical laboratory services; computer assisted diagnosis; primary health care; vitamin B12 deficiency
Corresponding author: Maria Salinas, PhD, Clinical Laboratory, Hospital Universitario de San Juan, Carretera Alicante-Valencia, s/n, 03550 San Juan de Alicante, Alicante, Spain; and Department of Biochemistry and Molecular Pathology, Universidad MiguelHernandez, Elche, Spain, Phone: +34 965169463, Fax: +34 965169460

Acknowledgments

The author thank Thermo Fischer Scientific which kindly provided APCA and IBFA detection tests.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The study was financially supported by Phadia GmbH, Freiburg, Germany.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. de Benoist B. Conclusions of a WHO Technical Consultation on Folate and Vitamin B12 Deficiencies. Food Nutr Bull 2008;29:S238–44.10.1177/15648265080292S129Search in Google Scholar PubMed

2. Baik HW, Russell RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr 1999;19:357–77.10.1146/annurev.nutr.19.1.357Search in Google Scholar PubMed

3. Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med 2000;51:357–75.10.1146/annurev.med.51.1.357Search in Google Scholar PubMed

4. Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr 1994;60:2–11.10.1093/ajcn/60.1.2Search in Google Scholar PubMed

5. Clarke R, Refsum H, Birks J, Evans JG, Johnston C, Sherliker P, et al. Screening for vitamin B-12 and folate deficiency in older persons. Am J Clin Nutr 2003;77:1241–7.10.1093/ajcn/77.5.1241Search in Google Scholar PubMed

6. Clarke R, Grimley Evans J, Schneede J, Nexo E, Bates C, Fletcher A, et al. Vitamin B12 and folate deficiency in later life. Age Ageing 2004;33:34–41.10.1093/ageing/afg109Search in Google Scholar PubMed

7. Loikas S, Koskinen P, Irjala K, Lopponen M, Isoaho R, Kivela S-L, et al. Vitamin B12 deficiency in the aged: a population-based study. Age 2007;36:177–83.10.1093/ageing/afl150Search in Google Scholar PubMed

8. Chui CH, Lau FY, Wong R, Soo OY, Lam CK, Lee PW, et al. Vitamin B12 deficiency – need for a new guideline. Nutrition 2001;17:917–20.10.1016/S0899-9007(01)00666-9Search in Google Scholar PubMed

9. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. J Am Med Assoc 2013;310:2435–42.10.1001/jama.2013.280490Search in Google Scholar PubMed

10. Spence JD. Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke. Nutr Res 2016;36:109–16.10.1016/j.nutres.2015.10.003Search in Google Scholar PubMed

11. Miranti EH, Stolzenberg-Solomon R, Weinstein SJ, Selhub J, Männistö S, Taylor PR, et al. Low vitamin B12 increases risk of gastric cancer: a prospective study of one-carbon metabolism nutrients and risk of upper gastrointestinal tract cancer. Int J Cancer 2017;141:1120–9.10.1002/ijc.30809Search in Google Scholar PubMed PubMed Central

12. Lachner C, Steinle NI, Regenold WT. The neuropsychiatry of vitamin B12 deficiency in elderly patients. J Neuropsychiatry Clin Neurosci 2012;24:5–15.10.1176/appi.neuropsych.11020052Search in Google Scholar PubMed

13. Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr 2009;89:693S–6S.10.3945/ajcn.2008.26947ASearch in Google Scholar PubMed

14. Salinas M, Flores E, López-Garrigós M, Leiva-Salinas M, Asencio A, Lugo J, et al. Computer-assisted interventions in the clinical laboratory process improve the diagnosis and treatment of severe vitamin B12 deficiency. Clin Chem Lab Med 2018;56:1469–75.10.1515/cclm-2017-1116Search in Google Scholar PubMed

15. Irvine WJ, Davies SH, Teitelbaum S, Delamore IW, Williams AW. The clinical and pathological significance of gastric parietal cell antibody. Ann N Y Acad Sci 1965;124:657–91.10.1111/j.1749-6632.1965.tb18993.xSearch in Google Scholar PubMed

16. Wright R, Whitehead R, Wangel AG, Salem SN, Schiller KF. Autoantibodies and microscopic appearance of gastric mucosa. Lancet 1966;1:618–21.10.1016/S0140-6736(66)90821-XSearch in Google Scholar PubMed

17. Rusak E, Chobot A, Krzywicka A, Wenzlau J. Anti-parietal cell antibodies – diagnostic significance. Adv Med Sci 2016;61:175–9.10.1016/j.advms.2015.12.004Search in Google Scholar PubMed

18. Bizzaro N, Antico A. Diagnosis and classification of pernicious anemia. Autoimmun Rev 2014;13:565–8.10.1016/j.autrev.2014.01.042Search in Google Scholar PubMed

19. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med 1999;159:1289–98.10.1001/archinte.159.12.1289Search in Google Scholar PubMed

20. Park JY, Lam-Himlin D, Vemulapalli R. Review of autoimmune metaplastic atrophic gastritis. Gastrointest Endosc 2013;77:284–92.10.1016/j.gie.2012.09.033Search in Google Scholar PubMed

21. Hannibal L, Lysne V, Bjørke-Monsen A-L, Behringer S, Grünert SC, Spiekerkoetter U, et al. Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency. Front Mol Biosci 2016;3:27.10.3389/fmolb.2016.00027Search in Google Scholar PubMed PubMed Central

22. Murphy G, Dawsey SM, Engels EA, Ricker W, Parsons R, Etemadi A, et al. Cancer risk after pernicious anemia in the US elderly population. Clin Gastroenterol Hepatol 2015;13:2282–9.e4.10.1016/j.cgh.2015.05.040Search in Google Scholar PubMed PubMed Central

23. Allum WH, Blazeby JM, Griffin SM, Cunningham D, Jankowski JA, Wong R, et al. Guidelines for the management of oesophageal and gastric cancer. Gut 2011;60:1449–72.10.1136/gut.2010.228254Search in Google Scholar PubMed

Received: 2019-07-22
Accepted: 2019-09-05
Published Online: 2019-11-12
Published in Print: 2020-02-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Progress in understanding the use of human chorionic gonadotropin as a tumor marker
  4. Reviews
  5. Biomarkers for prostate cancer: prostate-specific antigen and beyond
  6. Gut microbiome investigation in celiac disease: from methods to its pathogenetic role
  7. Opinion Papers
  8. Understanding and managing interferences in clinical laboratory assays: the role of laboratory professionals
  9. A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer
  10. EFLM Opinion Paper
  11. Validation and verification of examination procedures in medical laboratories: opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation
  12. Guidelines and Recommendations
  13. An updated protocol based on CLSI document C37 for preparation of off-the-clot serum from individual units for use alone or to prepare commutable pooled serum reference materials
  14. General Clinical Chemistry and Laboratory Medicine
  15. Highly accurate and explainable detection of specimen mix-up using a machine learning model
  16. Impact of delta check time intervals on error detection capability
  17. Effect of long-term frozen storage and thawing of stool samples on faecal haemoglobin concentration and diagnostic performance of faecal immunochemical tests
  18. A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers
  19. Macro vitamin B12: an underestimated threat
  20. Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients
  21. High frequency of anti-parietal cell antibody (APCA) and intrinsic factor blocking antibody (IFBA) in individuals with severe vitamin B12 deficiency – an observational study in primary care patients
  22. DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients
  23. Cancer Diagnostics
  24. How comparable are total human chorionic gonadotropin (hCGt) tumour markers assays?
  25. Diabetes
  26. Measurement accuracy of two professional-use systems for point-of-care testing of blood glucose
  27. Letters to the Editor
  28. Human chorionic gonadotropin in oncology: a matter of tight (bio)marking
  29. More robust analytical evidence should support the selection of human chorionic gonadotropin assays for oncology application
  30. Letter in reply to the letter to the editor of Ferraro S and Panteghini M with the title “More robust analytical evidence should support the selection for human chorionic gonadotropin assays for oncology application”
  31. Definition of analytical quality specifications for serum total folate measurements using a simulation outcome-based model
  32. Alarmed by misleading interference in free T3 and free T4 assays: a new case of anti-streptavidin antibodies
  33. A root cause analysis of ‘falsely elevated’ oxygen saturation: investigation of pneumatic tube transport and differences between estimated and measured saturation in a critical patient population
  34. The chaos of serologic markers in interstitial pneumonia with autoimmune features can be corrected by the laboratory physician
  35. Vitamin A and E gender and age stratification in adults
  36. Detection of monoclonal B-lymphocytosis: interest of cellular population data and CytoDiff™ analysis
  37. Urinary reference intervals for gadolinium in individuals without recent exposure to gadolinium-based contrast agents
  38. Molecular diagnosis of toxoplasmosis: evaluation of automated DNA extraction using eMAG® (bioMérieux) on buffy coat, cerebrospinal and bronchoalveolar lavage fluids
  39. Retraction
  40. Retraction of: The Effect of a Gender Difference in the Apolipoprotein E Gene DNA Polymorphism on Serum Lipid Levels in a Serbian Healthy Population
https://doi.org/10.1515/cclm-2019-0749
Keywords for this article
clinical laboratory services; computer assisted diagnosis; primary health care; vitamin B12 deficiency

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Progress in understanding the use of human chorionic gonadotropin as a tumor marker
  4. Reviews
  5. Biomarkers for prostate cancer: prostate-specific antigen and beyond
  6. Gut microbiome investigation in celiac disease: from methods to its pathogenetic role
  7. Opinion Papers
  8. Understanding and managing interferences in clinical laboratory assays: the role of laboratory professionals
  9. A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer
  10. EFLM Opinion Paper
  11. Validation and verification of examination procedures in medical laboratories: opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation
  12. Guidelines and Recommendations
  13. An updated protocol based on CLSI document C37 for preparation of off-the-clot serum from individual units for use alone or to prepare commutable pooled serum reference materials
  14. General Clinical Chemistry and Laboratory Medicine
  15. Highly accurate and explainable detection of specimen mix-up using a machine learning model
  16. Impact of delta check time intervals on error detection capability
  17. Effect of long-term frozen storage and thawing of stool samples on faecal haemoglobin concentration and diagnostic performance of faecal immunochemical tests
  18. A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers
  19. Macro vitamin B12: an underestimated threat
  20. Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients
  21. High frequency of anti-parietal cell antibody (APCA) and intrinsic factor blocking antibody (IFBA) in individuals with severe vitamin B12 deficiency – an observational study in primary care patients
  22. DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients
  23. Cancer Diagnostics
  24. How comparable are total human chorionic gonadotropin (hCGt) tumour markers assays?
  25. Diabetes
  26. Measurement accuracy of two professional-use systems for point-of-care testing of blood glucose
  27. Letters to the Editor
  28. Human chorionic gonadotropin in oncology: a matter of tight (bio)marking
  29. More robust analytical evidence should support the selection of human chorionic gonadotropin assays for oncology application
  30. Letter in reply to the letter to the editor of Ferraro S and Panteghini M with the title “More robust analytical evidence should support the selection for human chorionic gonadotropin assays for oncology application”
  31. Definition of analytical quality specifications for serum total folate measurements using a simulation outcome-based model
  32. Alarmed by misleading interference in free T3 and free T4 assays: a new case of anti-streptavidin antibodies
  33. A root cause analysis of ‘falsely elevated’ oxygen saturation: investigation of pneumatic tube transport and differences between estimated and measured saturation in a critical patient population
  34. The chaos of serologic markers in interstitial pneumonia with autoimmune features can be corrected by the laboratory physician
  35. Vitamin A and E gender and age stratification in adults
  36. Detection of monoclonal B-lymphocytosis: interest of cellular population data and CytoDiff™ analysis
  37. Urinary reference intervals for gadolinium in individuals without recent exposure to gadolinium-based contrast agents
  38. Molecular diagnosis of toxoplasmosis: evaluation of automated DNA extraction using eMAG® (bioMérieux) on buffy coat, cerebrospinal and bronchoalveolar lavage fluids
  39. Retraction
  40. Retraction of: The Effect of a Gender Difference in the Apolipoprotein E Gene DNA Polymorphism on Serum Lipid Levels in a Serbian Healthy Population
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 8.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2019-0749/html
Scroll to top button