In PA patients, antibodies form to attack either the IF (Intrinsic Factor, a protein in the stomach needed for the absorption of B12), or the gastric parietal cells, which produce IF in first place. Therefore, the two types of Pernicious Anemia antibodies are the gastric parietal cell antibodies and the IF antibodies. Let’s have a look at both.
Gastric Parietal Cell Antibodies (GPCA)
The gastric parietal cells (GPCs) line the wall of our stomach. They specialize in secreting Intrinsic Factor, and creating gastric acid to help with food digestion. When you digest food, the acid produced by GPCs separates the B12 from the food. The free B12 then binds to IF to form a unique complex that can now move to the small intestine.
When the immune system is producing antibodies to parietal cells (by error, of course), the inevitable destruction of the cells sets in. This results in diminished (or completely absent) gastric acid and IF production, and thus impaired ability to absorb B12. Since B12 is vital for making red blood cells, anemia soon takes place.
GPC antibodies (GPCAs) exist in ~80%–90% of PA patients, usually in early stages of the disease. In later stages, the incidence of those antibodies decrease as a result of the progressive loss of GPC mass. Only around 55% of people with advanced PA show any anti gastric parietal cell antibodies. Thus, the absence of GPCAs doesn’t omit PA.
But, if you test positive (auto gastric parietal cell antibodies), what does it suggest? Not necessarily that you have Pernicious Anemia. That’s because GPCAs are unspecific to PA and can exist in a whole host of other autoimmune disorders, like Hashimoto’s disease or diabetes. Low levels of these antibodies can also be found in ~5% of healthy people.
In other words, most people with Pernicious Anemia will have GPCAs, but not everyone with GPCAs will have Pernicious Anemia. Well, at least not yet. Because testing positive for GPCAs does mean you’re 90%+ likely to have Autoimmune Atrophic Gastritis, which may end up in PA as time goes on and once enough parietal cells have been damaged.
Intrinsic Factor Antibodies (IFA)
Your body can only absorb B12 after it has bound to IF, creating the complex that moves the B12 to the small intestine. In the ileum it binds to receptors that carry it through the intestinal wall into the bloodstream, where it binds to transcobalamin. It ends up in the tissues and cells and takes the form of either methylcobalamin or adenosylcobalamin.
In other words: No IF = No B12 taken in.
Unlike GPCAs, antibodies against Intrinsic Factor are highly specific. They rarely exist in any disease other than Pernicious Anemia. We say rarely, because they were found in some cases of thyroid disease with a non progressive atrophic gastritis and a normal IF production. Same goes for rheumatoid arthritis, though sufferers may develop PA later.
Still, IFAs are so specific to PA that their presence confirms diagnosis. Better safe than sorry! Remember, PA treatment is simple and risk-free. Anyway, the lack of IFAs cannot omit PA, since only ~50% of PA patients (some say 70%) test positive.
There are two types of IFAs:
Type I: Blocking antibodies. These inhibit B12 from binding to IF, blocking the formation of the B12/IF complex that is meant to carry the B12 to the small intestine.
Type II: Binding antibodies. These bind to the B12/IF complex and thwart its absorption. They exist almost only in those who already have type I antibodies, which is why doctors will normally test just for type I.
Pernicious Anemia Antibody Test
Antibodies in Pernicious Anemia are easy to test for with a blood sample. If your B12 levels are low, or if your MMA (methylmalonic acid) or homocysteine levels are high (even more so if you show signs of Pernicious Anemia), those tests can confirm diagnosis.
If you test positive for both anti Intrinsic Factor antibodies and anti parietal cell antibodies, you will be diagnosed with Pernicious Anemia. This is the most definitive diagnostic case. However, some people will test positive for just IFAs or just GPCAs. But even if you test positive for just one of them, doctors may still diagnose you with PA.
Remember, B12 shots (the only way to treat PA) pose no risk. B12 is water soluble, so any excess is flushed out through the urine. And so, for borderline cases, it is much safer to give a positive diagnosis ‘just in case’ and start treatment right away.
If one of the tests comes back negative, you still can’t exclude PA. Again, at least 10% of those with PA will not have GPCAs (number is higher in later stages as a result of GPC mass loss). And at least 30% will not have IFAs in their blood.
To understand your test results, we advise to read our page about PA diagnosis.
Important: Don’t do the antibodies test if you supplemented with B12 within the last 72 hours, or if you received a B12 injection within the last two weeks. High serum B12 levels may interfere and lead to false positive results.
How accurate are the tests?
The novel ELISA assay yields a sensitivity of 37% and specificity of 100% for IFAs, with 81.5% sensitivity and 90.3% specificity for GPCAs. Combining them significantly boosts their diagnostic performance, giving 73% sensitivity and 100% specificity.
So please do them both!