In individuals with Pernicious Anemia antibodies form to attack the Intrinsic Factor (a protein in the stomach necessary for the utilization and absorption of vitamin B12), or the cells that produce Intrinsic Factor in first place, the Gastric Parietal Cells.
Therefore, the two types of Pernicious Anemia antibodies are the anti parietal and Intrinsic Factor antibodies. Let’s have a look at each of them.
Anti Gastric Parietal Cell Antibodies
Also known as Parietal Cell Antibody, Gastric Parietal Cell Antibody, Anti-parietal Cell Antibody, Anti-GPA, AGPA, APCA, IgG.
The parietal cells are cells that line up the wall of our stomach. They specialize in producing Intrinsic Factor and creating acid to help with food digestion. When our immune system create Gastric Parietal Cell Antibodies, those autoantibodies (antibodies that our body creates by error), those cells are now under attack.
When you digest food, the stomach acids produced by the parietal cells release the B12 from the food, which then binds to Intrinsic Factor to form a unique complex, which allows the B12 to move to the small intestine.
Anti-GPC antibodies are present at a high frequency of approximately 80%–90%, especially in early stages of the disease. However, they are unspecific to Pernicious Anemia and can be found at other autoimmune conditions (like Hashimoto’s disease or diabetes) or generally in elder people, even those free of any atrophic gastritis. In later stages of Pernicious Anemia, the incidence of those antibodies decrease as a result of progression and the loss of GPC mass. About 55% of patients with advanced Pernicious Anemia test show incidence of anti gastric parietal cells antibodies.
“Tested positive auto gastric parietal cell antibodies what does it suggest?!”
If you do a Pernicious Anemia antibodies blood test and those antibodies are found, it doesn’t necessarily mean you have Pernicious Anemia… yet. Testing positive for parietal cell antibodies mean you’re more than 90% to have Autoimmune Atrophic Gastritis, a condition which may end up in Pernicious Anemia over time once enough parietal cells are damaged and the production of Intrinsic Factor is disrupted.
Patients with diabetes and thyroidism can have those antibodies too by the way. And ~10% of healthy people will test positive for it too! BUT, if your levels of B12 are low enough, most doctors will diagnose you with PA if you test positive for Gastric Parietal Cell Antibodies.
Also, at least 10% of those affected with Pernicious Anemia will not test positive for parietal cell antibodies. Keep that in mind!
90% of PA patients will have parietal cell antibodies, but not everybody with with those antibodies have PA. They can also be found in patients with diabetes, thyroiditis, gastritis, and a whole other host of autoimmune disorders. They may even be found in about %10 of the general healthy population!
Anti-GPC sensitivity is around 80% (80% of those who test positive have PA, although some say it’s as low as 50%), while specificity is higher than 90% (>90% of those who test negative do not have PA).
Antibodies Against Intrinsic Factor
B12 can only be absorbed when it binds to Intrinsic Factor in the first part of the small intestine, creating a complex that then moves further to the allium, where it binds itself to the receptors. From there the vitamin is transported through the intestinal wall, and in the blood stream it binds to trasncobalamn, which brings it further to the tissues and cells where it becomes either methylcobalamin or adenosylcobalamin.
Intrinsic Factor antibodies are more specific than parietal cell antibodies. They only occur in the case of Pernicious Anemia, and have a well-documented role in the onset of this condition, through the deficiency of B12 that they induce.
There are two types of IF antibodies:
Type I: Blocking antibodies. Those inhibit vitamin B12 from binding to Intrinsic Factor, preventing the formation of the B12/IF complex that is supposed to be transferred to the small intestine.
Type II: Binding antibodies. Those bind to the B12/IF complex and prevent its absorption. Those are found in ~33% of patients, and only in those who already have type I blocking antibodies, which is why you’ll usually be tested only for type I antibodies.
Specificity for IF antibodies is 100%, meaning if you do not those antibodies you do not have Pernicious Anemia. Sensitivity is around 35-50%, meaning only 35-50% of those who test positive has PA. The presence of antibodies against Intrinsic Factor concludes a diagnosis of PA. However, a negative test result cannot omit Pernicious Anemia.
Pernicious Anemia Antibodies Results
If you test positive for parietal cell antibodies Pernicious Anemia
If you test positive for both Intrinsic Factor antibodies and parietal cell antibodies, you will have a Pernicious Anemia diagnosis.
Testing for those two antibodies is done through a blood sample. It should be quickly done as follow-up tests when a patient shows low B12 levels and increased methylmalonic acid (MMA) and homocysteine levels. If the patient shows symptoms of Pernicious Anemia, those tests can confirm diagnosis.
If your B12 levels are low, your MMA & homocysteine levels are high, and you test positive for either IF or GPC antibodies, you are very likely to have Pernicious Anemia. The combination of both anti parietal and Intrinsic Factor antibodies yield 73% sensitivity and 100% specificity.