What is the main cause of pernicious anemia?

January 1, 2026 •

2 min read

According to the National Institutes of Health, pernicious anemia is a relatively rare autoimmune disorder that diminishes dietary vitamin B12 absorption. The main cause of pernicious anemia is an autoimmune attack on the stomach's cells, leading to intrinsic factor deficiency and subsequent B12 malabsorption.

Quick Summary

Pernicious anemia is an autoimmune disorder where the immune system attacks the stomach's parietal cells, causing a deficiency of intrinsic factor. This leads to the malabsorption of vitamin B12, ultimately resulting in megaloblastic anemia.

Key Points

Autoimmune Root: The primary cause of pernicious anemia is an autoimmune reaction where the body's immune system attacks its own healthy stomach cells.
Intrinsic Factor Deficiency: The autoimmune attack destroys gastric parietal cells, which are responsible for producing intrinsic factor, a protein vital for B12 absorption.
Vitamin B12 Malabsorption: Without intrinsic factor, the body cannot absorb vitamin B12 from the small intestine, leading to a profound deficiency.
Neurological Consequences: Untreated pernicious anemia can lead to severe and potentially irreversible neurological damage, including peripheral neuropathy, confusion, and memory loss.
Lifelong Treatment: The condition is not curable but is manageable with lifelong vitamin B12 supplementation, typically through injections, to bypass the absorption problem.
Associated Conditions: Patients with pernicious anemia often have other autoimmune conditions, including Type 1 diabetes and thyroid diseases, suggesting a shared susceptibility.
Increased Cancer Risk: The chronic inflammation from autoimmune gastritis is associated with a higher risk of stomach cancer.

The Autoimmune Attack: The Root Cause of Pernicious Anemia

The primary cause of pernicious anemia is an autoimmune response. The body's immune system attacks cells in the stomach lining that produce intrinsic factor, a protein essential for absorbing vitamin B12. This leads to a severe vitamin B12 deficiency and megaloblastic anemia.

The Role of Intrinsic Factor in Vitamin B12 Absorption

Vitamin B12 is found mainly in animal products. Its absorption involves several steps:

Release from food aided by stomach acid.
Binding to intrinsic factor produced by parietal cells.
Absorption of the intrinsic factor-B12 complex in the small intestine.

Pernicious anemia disrupts this process by destroying parietal cells, preventing intrinsic factor production and thus B12 absorption.

Symptoms and Risk Factors

Symptoms are often subtle and worsen over time.

Common Symptoms

General: Fatigue, lack of energy, and lightheadedness.
Neurological: Numbness, tingling, memory issues, and balance problems.
Gastrointestinal: Nausea, appetite loss, weight loss, and a swollen tongue.
Hematological: Pale skin and mild jaundice.

Key Risk Factors

Risk factors include:

Other Autoimmune Diseases: Conditions like Type 1 diabetes and thyroid disease increase risk.
Genetics: A family history is a factor.
Age: More common over 60.
Ethnicity: Higher prevalence in people of Northern European descent.

Diagnosis and Treatment

Diagnosis involves clinical assessment and lab tests. Treatment is lifelong B12 supplementation.

Diagnostic Process

Blood Tests: CBC shows macrocytic anemia; B12 levels are low.
Antibody Testing: Detection of anti-intrinsic factor and anti-parietal cell antibodies.
MMA and Homocysteine: Elevated levels can confirm deficiency.

Treatment Approach

As oral absorption is impaired, treatment bypasses this pathway.

Injections: Initial frequent B12 injections followed by monthly maintenance.
High-Dose Oral: May be effective in some cases as minimal B12 can be absorbed without intrinsic factor.

Pernicious Anemia vs. Other B12 Deficiency Causes

Differentiating pernicious anemia from other causes is crucial. The table below highlights some key differences.


Feature	Pernicious Anemia	Dietary B12 Deficiency	Other Malabsorption Issues
Primary Cause	Autoimmune attack on stomach cells	Inadequate B12 intake	GI diseases or surgery
Intrinsic Factor	Severely deficient	Normal production	Normal unless stomach affected
Antibodies	Present	Not typically present	Not typically present
Onset	Slow, over many years	Can be quicker	Varies by condition
Treatment Method	Primarily injections	Oral supplements usually sufficient	Treat underlying condition, supplements may be needed

Conclusion

The main cause of pernicious anemia is an autoimmune attack preventing vitamin B12 absorption. This distinct B12 deficiency differs from other causes. Lifelong B12 supplementation effectively manages the condition. Early detection and treatment adherence are vital to prevent severe neurological and other complications. Understanding the autoimmune basis of pernicious anemia is important. For more details on vitamin B12 deficiency, visit the Cleveland Clinic website.

Frequently Asked Questions

The key protein affected in pernicious anemia is intrinsic factor, which is produced by the parietal cells in the stomach. The body's immune system attacks these cells, causing a deficiency of intrinsic factor and blocking vitamin B12 absorption.

No, while dietary insufficiency of vitamin B12 can cause B12 deficiency anemia, it is not the main cause of pernicious anemia itself. Pernicious anemia is specifically an autoimmune condition. However, a poor diet is a risk factor for general B12 deficiency.

Oral vitamin B12 is often ineffective for treating pernicious anemia because the condition prevents the absorption of B12 through the digestive tract due to the lack of intrinsic factor. Injections are typically required to bypass this absorption problem.

Common symptoms include fatigue, weakness, a smooth or sore tongue, pale skin, weight loss, and neurological issues like numbness or tingling in the hands and feet, confusion, and memory problems.

Diagnosis involves several blood tests, including a complete blood count (CBC) to check for macrocytic anemia, a serum vitamin B12 level test, and tests for anti-intrinsic factor and anti-parietal cell antibodies.

If left untreated, pernicious anemia can cause severe, irreversible neurological damage, heart problems, and increase the risk of developing certain cancers, such as stomach cancer.

While it is not strictly genetic, there appears to be a genetic predisposition. There is a higher risk of developing pernicious anemia if other family members also have the condition.