What is the sensitivity and specificity of anti-intrinsic factor (Anti-IF) antibodies versus anti-parietal cell (Anti-PC) antibodies for diagnosing pernicious anemia?

From the Guidelines

Anti-intrinsic factor antibodies are the preferred diagnostic test for pernicious anemia due to their high specificity, as recommended by the latest guidelines 1. When evaluating a patient with suspected pernicious anemia, it is essential to consider the sensitivity and specificity of anti-intrinsic factor antibodies (anti-IFAB) and anti-parietal cell antibodies.

• Anti-intrinsic factor antibodies have a specificity of approximately 95-100% but a sensitivity of only 50-70%, making them excellent for confirming pernicious anemia when present but not for ruling it out when absent.
• In contrast, anti-parietal cell antibodies have higher sensitivity (around 80-90%) but lower specificity (50-70%), as they can be found in other autoimmune conditions and in healthy elderly individuals. The latest guideline from the espen micronutrient guideline 1 recommends screening for pernicious anemia with the presence of anti-intrinsic factor antibodies (anti-IFAB) regardless of cobalamin levels, especially in patients with autoimmune diseases or with glossitis, anemia, and neuropathy. For optimal diagnostic accuracy, both antibody tests should be performed together, along with additional testing such as complete blood count, vitamin B12 levels, methylmalonic acid, and homocysteine levels, and potentially gastric biopsy to confirm atrophic gastritis 1. It is crucial to note that the British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma 1 provide recommendations on endoscopic surveillance and diagnosis of gastric adenocarcinoma, but they do not directly address the diagnostic accuracy of anti-intrinsic factor antibodies and anti-parietal cell antibodies for pernicious anemia. Therefore, when diagnosing pernicious anemia, it is recommended to prioritize anti-intrinsic factor antibodies due to their high specificity, as stated in the latest guideline 1.

From the Research

Sensitivity and Specificity of Anti-Intrinsic Factor Antibodies and Anti-Parietal Cells Antibodies

• The sensitivity of anti-parietal cell antibodies for pernicious anemia was found to be 68.2% with a specificity of 91.7% 2.
• The sensitivity of anti-intrinsic factor antibodies for pernicious anemia was found to be 40.9% with a specificity of 98.6% 2.
• When both antibodies were combined, the sensitivity and specificity rates were 86.36% and 90.28%, respectively 2.

Comparison of Antibody Prevalence

• Anti-parietal cell antibodies were found in 90% of patients with pernicious anemia, but have low specificity 3.
• Anti-intrinsic factor antibodies were found in only 60% of patients with pernicious anemia, but are considered highly specific for the disease 3.
• A study found that 57% of patients with severe vitamin B12 deficiency presented with antibodies to anti-parietal cell antibodies, and 14% presented with antibodies to intrinsic factor blocking antibodies 4.

Influence of Patient Age and Race

• The prevalence of anti-parietal cell antibody and anti-intrinsic factor antibody was found to vary with patient age and race 5.
• Anti-intrinsic factor antibody was found in 70% of patients, with blacks and Latin Americans having a significantly higher prevalence than whites 5.
• Patients lacking anti-parietal cell antibody were found to be significantly younger than those who had the antibody 5.

Diagnostic Value of Antibodies

• Testing for gastric parietal cell antibodies is an appropriate screening test for pernicious anemia, with intrinsic factor antibodies reserved for confirmatory testing or in patients with other autoantibodies that mask the gastric parietal cell pattern 6.
• The detection of both anti-parietal cell antibodies and anti-intrinsic factor antibodies is helpful in diagnosing pernicious anemia, and the combination of the two assays increases diagnostic sensitivity 2.