I’m wondering about the anti IFAB test. I am aware that only 50% of people with PA test positive for these, but not sure why.
Does anyone know if it’s just your luck on the day (I.e. do antibody levels fluctuate significantly, possibly when you are having a gastritis flare - I’ve got anti parietal cell antibodies) or is it that your condition might not be progressed enough? Or is it just that the blood test accuracy is poor?
I’ve had a test result of 1 and it needs to be over 1.2 to be considered positive. I’m not sure whether it’s a result that gets bigger over time as you get worse (and therefore worth waiting a while and testing again) or if it’s like roulette with a 50/50 chance each time.
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With fluctuations it’s probably worth testing again at some point in the future then - hopefully before my parietal cells are too damaged and are unable to produce any IF!
PS to my previous post: In order to determine whether provisional B12 treatment is effective, the first step is to do a thorough survey of symptoms. Here, again, the medical research literature is less than helpful due to lack of quality research. My suggestion is as follows:
1. Go to the Pernicious Anemia Society website symptoms page.
2. Copy the symptoms, paste into a word processor, and convert it to a symptom checklist.
3. Select the symptoms you have.
4. Indicate, specifically as possible, the severity of each one, eg, level of pain, level of limitations, frequency, and anything else that helps to specifically indicate a baseline.
5. After treatment, use the list to note two categories of improvement
a. Degree of improvement
b. Comparison of current state to "normal"
The reason for maintaining the two categories is twofold:
1. if improvement occurs with treatment, you want to be able to demonstrate that.
2. Guidelines say to continue treatment (ie, injections, at a given amount and frequency) "until no further improvement occurs". For many people, especially with symptoms that have developed over many months or years, improvement occurs, but slowly. Some doctors look at slowed improvement as "stopped" improvement and will push for prematurely reduced levels of treatment.
The old adage, 'Treat the patient, not the numbers' works here. And 'listen to the patient telling you the diagnosis'. The doctors who can't grasp those simple rules don't derserve the role.
The Schilling Test [or 'tests' to be more precise] were complex. The test measured the ability to absorb B12. Here's how it went.
Patient with low serum B12:
1.Start by treating the patient with B12 injections to get them to B12-replete status.
2.Give them B12 injection to saturate the transcobalamins. [Important!]
3.Give them a capsule containing radioactive B12 [the cobalt atom in the B12 molecule is a radioisotope of cobalt, so we can detect it later.]
4.Send them home with a uring container and instructions to collect every last drop of urine they pass in the next 24 hours.
5.Bring the urine back, measure the volume and count the radioactivity excreted.
6.Calculate the urine radioactivity as a % of the total ingested. [The excess, absorbed, is excreted faecally.]
repeat all the above steps with another capsule, this time containing radioactive B12 bound to IF.
Express the ratio of the second part to the first part.
If the absorption of Radioactive B12 is the same in the bound and unbound, then there's no absorption problem. If however there's a higher proportion of 'bound' absorbed then the IF has facilitated this, and it looks like PA.
As you can see, the whole process is going to take several weeks/months, a lot of patient time, a lot of lab time and considerable cost.
A lab measuring IFAb can do hundreds in a day, but only find 50% of those who can't absorb. A lab performing the Schilling test could do one or two per day in reality, at very considerable cost. All that, and the test wasn't infallible. If the patient didn't collect all of the 24 hour urine then the result would be incorrect. If they did, but spilled some, ditto.
The DiCoPac test was a smart development. It used two different Cobalt isotopes, with different emission spectra, so we could do it all in one visit, but step 1 able was still vital.
That is such an informative thread. Thank you for sharing, I read it when there were only a few responses and didn’t realise it had kept going. I can see people have experienced all 3 of these potential issues plus the fact there might be little or no IF being produced.
Inspired by this I looked back on my mother's results - she recently had a positive IFAB test. 5 years ago she had IFAB tested and it was negative. I've had, I think, 3 tests and so far all negative. Perhaps I'll have to wait until I'm her age LOL.
Thank you for checking. I really appreciate it. Waiting for old age - that’s exactly what I’m worried about. My mum was v ill before her b12 deficiency showed in her blood and her neurological damage was irreversible. I am absolutely determined to work out this puzzle before I get to that stage! I hope you do too!
I haven't figured out the puzzle unfortunately, just been self injecting with great success But that's what I mean - if I hadn't started SI 6 years ago, i would literally be dead by now. Without ever have gotten a positive IFAB test lol.
Are you saying that you are being forced to wait for a positive antibody test before you can be treated? If so, that is bad medicine. (No pun intended.) B12 deficiency with neural symptoms is a clinical diagnosis, ie, if there are symptoms accompanied by ambiguity, the "test" is to frequently (eg, every other day, or twice each week) inject B12 for two or three months, then look to see whether symptoms have improved. Since the idea is to check for symptom improvement with B12 treatment, I personally think every other day, or even every day, is the wise choice, since, due to lack of research, no one knows the optimal dose size or frequency, and B12 is not toxic at any level,so there is no point in choosing a treatment level that might continue ambiguity.
For more information, a good source is the research summary article, "The Many Faces of Cobalamin (B12) Deficiency".
Didn't someone say that if you're injecting B12 that you should stop before you take an ifab or PCAB test? Does perhaps that interfere? I'm just learning all this but my pcab test came back in a mid-range it wasn't positive or negative but because I had a positive ifab and also megaoblastic anemia that my pcab should be considered positive even though it's somewhere in between. So I was wondering if maybe because your other tests came out to point towards pernicious anemia that perhaps this mid-range area that you fall in, I call them a crack, could be interpreted as positive? I don't know I'm just wondering.
B12 can interfere with IFAB but not GPCAB as far as I know. For IFAB, what happens is that if B12 levels are high, it can give a false-positive IFAB results. That is, the test will say you have the antibodies when in face you don't actually have them.
But this interference will not give a false-negative (the test says you don't have antibodies, when you actually do).
As discussed above, you may still have a negative result even though you have PA, because it really is a false negative, or antibodies aren't active, or for a bunch of other reasons no one really seems to know.
We've had several 'borderline' results between myself and my sister as well - cutoff is 1.1 and we get 1.0. It's still technically classed as negative but I also wonder if it's not just a weak positive!
I don't think any of this applies to GPCAB - that's a different story altogether, because these antibodies appear in people with other autoimmune diseases without necessarily having PA.
I have low b12 (Not low enough for diagnosis!) so that’s definitely not interfering with my iFAB test. I wondered the same thing as you and your sister - about whether the 1.0 score was a weak positive rather than a weak negative. After reading all the comments I think it’s probably worth getting a private test done again in the future to check for any trends.
I've gone 6 years without ever getting a positive IFAB but with neuro symptoms so severe that if I had waited any longer, they would've probably been permanent. It's why i had to go the SI route.
I see your mother has PA and you have symptoms going back a while. Combined with low B12, it seems malpractice for them to make you wait.
If i were in your shoes and knew then what i know now, I wouldn't wait for docs to get a clue. Unless you can find a specialist that will treat you based on symptoms, or your b12 gets low enough (and even then they'll likely give tablets), you'll likely just get worse & worse.
Sorry to butt in. I am in the same situation. Low B12 plus neuro symptoms I need B12 jabs but still unable to find a company willing to ship to new customers in the uk.
Hi cheriton i replied to your other post and I think wedgewood sent you a PM (chat message). There are plenty of German pharmacies willing to ship to England & we can help you find what you need but we need more info. What brand or form of b12 eg hydroxo or cyano, 1ml or 2ml, can you do paypal or credit card or bank transfer? Do you need syringes & needles? Do you want to do IM (intramuscular) or subcutaneous (SC or subcut)? If you answer these questions we can send you exact details of which pharmacy etc.
Do you have someone to help you order? Wedgewood's instructions are very complete so if you're still struggling i would enlist someone to help you.
I think you are right about the crack. Sadly the GPs I have seen don’t seem to believe it exists. I couldn’t get my gp to test me for anything apart from b12 (which is low but not low enough to allow other tests to be ordered) despite obvious symptoms, other autoimmune diseases, and a parent with PA. They are happy to send me for ultrasounds, MRIs etc which cost a fortune but not for a therapeutic b12 trial. It’s a weird old thing.I’m going to have to give up on believing blood tests will provide the answers and have a proper argument (not usually my style!).
The test doesn't have a threshold of 0 because it picks up other metabolites as well as IFABThe threshold is set at whatever - they are arbitrary units set by the calibration of the machine - generally somewhere around 1 because this is trying to rule out the false positives that are caused by confusion with these other metabolites. If you get a significant response above this level then it is extremely unlikely that you don't have PA. A reading below this level is just an inconclusive test.
In lab speak the test is quite specific (not likely to indicate PA when PA isn't present) but it isn't very sensitive (may not pick up PA when PA is present). It is the fact that it is quite specific that makes it a useful test.
If you are looking to private testing to confirm PA then you may be better of looking at the possibility of a gastrin test, which seems to be better both specific and sensitive.
Scientist, not medic. Done thousands of these tests.
Antibody levels rise and fall with time. Various stimuli can affect this. [Get bitten by a horse fly and you'll find out; it can trigger a fairly broad non-specific immune reaction.]
Some patients quite possibly never actually produce IFAb regardless. So it's not the test that's not 'accurate'. If the antibodies aren't there, then the test won't find them.
I personally have a problem with reporting figures for the test. Figures of what? There's no International Standard for IFAb [or there wasn't when I was doing them] and I suspect there still won't be. [It's like nailing jelly to a wall.] Giving numbers to something like this is adding pseudo-precision to the test. Sorry, but that's how it is.
Re: the fluctuations, I was wondering more about whether IFABs are like thyroid hormones which go up and down quite materially over a 24hr cycle, but it sounds like IFABs are not like that - more a case of changing over a longer period. Am I understanding correctly?
Hi Sparkly [love the name!] I honestly can't say if there's diurnal variation in IFAb titres. If I was still working and had a tame PA patient with IFAb I'd be happy to sit them down, take blood every couple of hours and test them, publish the findingsand bask in the glory, but thankfully, I'm retired and have no wish to go back to that. There's an awful lot of dodgy publications out there. I would not be surprised if there was some variation, but not as regular as with thyroid. I have no info to back that up!
I'm in the U.S. (Oregon) and was IFAb tested. The lab didn't provide a numerical test value to the doctor or to me; the only test result options were "positive" or"negative". Mine was positive.
I would love to see Oregon at some stage. My only connection so far with the state has been a dried sourdough starter from 'The Oregon Trail.'Don't get me started about bread!
The question is simple, but the answer is fairly complicated and difficult to pull out of all the literature that is out there.
Firstly, if you truly have PA then you WILL have both Parietal Cell and intrinsic factor antibodies. The issue is finding those little buggers.
The sensitivity for IFAB tests are purposely set to a low sensitivity to exclude a host of erroneous indications. I apologize but I will have to dig through my research and get the description later. The sensitivity is set low so when you get a positive it is definitely positive. If you follow the pre test patient pre of-course which is discuss below. If you have a negative test result it does not mean you do not have IFABs floating around just that the has to do with the sensitivity of the test. Neither IFAB or PCAB positives are diagnostic of PA by themselves but rather are indicative and should be considered along with all your other symptoms. Two tests that are diagnostic are PCAB and high gastrin. But that will only be the case for advanced cases of PA where you have low/no gastric acid.
Regarding the question of do antibodies go away over time. They never go away but they do lesson in advanced stages of PA/AIG where most all of the Parietal Cells are destroyed and those antibodies have nothing left to attack it tames your immune system somewhat.
There are many, like 10, different test methods that different labs use to detect IFA. Some of these are Euroimmun ELISA, Bluedriver, Alegra, Euroimmun IIF, and a newer one EliA to name some of them.
The Bluedriver and IIF being the less sensitive
IFAB Tests are vulnerable to give false positive results if you have had a recent cobalamin injection. Manufacturer product literature warns that these assays are only suitable for samples with a specified upper limit of serum cobalamin levels, and laboratories must comply with this advice. However, true immunoassays for IFAB, based on porcine or recombinant intrinsic factor binding, can be used for post-treatment samples.
The two assays that use Porcine as the source are ELISA and IIF. Porcine is Pig Gastric Mucosa and I am absolutely not qualified to discuss the mechanics of how they use that in an immunoassay.
Also. Beware some of these require fasting for 8 hours prior to the blood draw.
Most doctors when they order your test do not know this. Most labs whether they are in hospital or external labs do ask if you have been fasting and for how long. But they do not ask if you have been supplementing with B12.
So, it is up to us to contact the lab or have a discussion with the hospital lab before they draw blood what their patient prep requirements are for their specific test method.
For external labs in US such as LabCorp or Quest Diagnostics you can find these at
“Patient should be fasting for 8 hours. This test should not be performed on patients who have received a vitamin B12 injection or radiolabeled vitamin B12 injection within the previous 2 weeks.”
The same holds true for PCAB testing, always check for type of test method and patient prep requirements. For example, LabCorp PCAB test…
shows method as Enzyme-linked Immunosorbent Assay (ELISA) but no patient prep requirements for having no B12 injections for some period of time prior to the test. Remember above that ELISA uses porcine as the source which is recommended for post B12 therapy testing.
Anyway, that’s a lot of rambling but hope it is helpful. Rex
Hi Rex, great writeup! I would just quibble over 2 remarks.
Firstly, if you truly have PA then you WILL have both Parietal Cell and intrinsic factor antibodies.
I don't think it's been established that those with PA will always have GPC Abs. There is at least 1 member here who along with her family are all IFab + and GPCab - and have no corresponding stomach issues. (Can't remember who though!). Likewise I haven't seen definite stats in the literature but am open to correction
Neither IFAB or PCAB positives are diagnostic of PA by themselves
I think it's generally accepted that if you test positive for IFAB, you will have a diagnosis of PA. Barring any interference from high b12 levels and getting a false positive - and the latest systems are very robust against this - you will have PA if IFAB is positive. Maybe we're just splitting hairs. Could you clarify what you mean? Because if you're right, we're all in big trouble! It means they can say you don't have PA even when IFAB +.
Jade_s, I apologize for my delayed response but it has been a busy week for me.
Just wanted to let you know that I love that you quibble over my statements on this because questioning is something we all need to do especially with this wonderful PA that we've been given.
Regarding your comment on my statement "Firstly, if you truly have PA then you WILL have both Parietal Cell and intrinsic factor antibodies." You are correct, I've never found a statement in all my research that specifically states that. So, I should have prefaced that with it was my own opinion. But that opinion is based on many research papers that say that PA is caused by the destruction of the parietal cells and intrinsic factor binding protein and/or binding site in the terminal ileum. That coupled with the statement in many medical research papers that 90% of those with PCAB have PA. and ~50% of those with PA will test positive for IFAB. So logically one could assume that those that test positive for IFAB do have PCAB. There are also those that TEST negative for IFAB but that does not mean they do not have IFAB or PA. There are those that test negative for IFAB but positive for PCAB like me. The key is we are talking test results and we know that the test results have some inaccuracies built in, especially for the IFAB at least for the negative results not the positive results. I have always had this question in the back of my mind... are there two types of PA/AIG? One where the Parietal Cells are not attacked but left untouched? But rather only the intrinsic factor binding protein is destroyed or the Ileal receptor is inhibited by the IFAB. The reason I wonder about this is that is seems some people with diagnosed PA have no gastric issues, I know them personally, but they do have the B12 deficiency issues. There are two paths of symptoms related to AIG...one is B12 deficient related and the other is Low/No gastric acid related and the whole host of digestive issues and possibility of gastric cancer. But my understanding is the Gastric issues related to the no gastric acid (achlorhydria) which I have comes later at an advanced stage of PA where all or most PCs are destroyed. It is also known that IFAB levels do increase as the disease progresses and reaches a more advanced state. There is a study where the trial participants that had PA we retested over a period of years and the actual IFAB positivity rate for this small trial increased from 50% to 80% suggesting that they had the IFAB previously but was not at a high enough level for the IFAB test to record that.
Regarding your second comment about my statement "Neither IFAB or PCAB positives are diagnostic of PA by themselves” I do stand by my statement here. I don’t think anyone that has been diagnosed with symptoms whether they have high B12 or not along with a positive IFAB test has any issue with their diagnosis. The key words in my statement are “by themselves”. There is plenty of literature that states these tests by themselves are indicative but not diagnostic. They must take into consideration other symptoms. IFAB is used to “confirm” a diagnosis not to diagnose by itself. In other words, you will need to have low serum B12, Megaloblastic Anemia, abnormal Homocysteine/MMA, or just high serum gastrin. Any of these plus a positive IFAB test is diagnostic of PA. The statement that a negative IFAB test does not preclude a PA diagnosis is true also but just indicates additional testing may be in order such as a positive PCAB and Gastrin is diagnostic of PA but either of those by itself is not.
One other reason that IFAB alone is not used BY ITSELF to diagnose any disorder is that, although IFAB is very specific to PA one can also show positive IFAB results for autoimmune thyroid disease and rheumatoid arthritis.
“Some patients with other autoimmune diseases may have positive IFBA assays without suffering from pernicious anemia (PA). This is reported particularly in patients with autoimmune thyroid disease or type I diabetes mellitus.”
The Lancet - international weekly general medical journal founded in 1823
“Antibody to gastric intrinsic factor was detected in the serum of seven women out of a series of eighty women and seventy men with insulin-dependent diabetes mellitus without pernicious anemia”
The European Journal of Internal Medicine suggests that “…clinical presentation and the combination of positive anti-intrinsic factor antibodies with upper endoscopy findings were highly suggestive of pernicious anaemia.”
“The results of intrinsic factor antibody (IF antibody) tests are often taken into consideration with the results of other laboratory tests to help make a diagnosis. When a person has a decreased vitamin B12 level and/or increased methylmalonic acid and homocysteine levels and has IF antibodies, then it is likely that the person has pernicious anemia.”
“The diagnosis of PA should be based on the combination of a thorough history, physical examination, careful examination of PBS and meticulous interpretation of laboratory tests. Elevated fasting serum gastrin and/or atrophic gastritis histopathology on gastric biopsy may help reach the diagnosis.”
The incidence of these antibodies rises with increasing duration of disease, almost doubling after 10 years (Ungar et al., 1967).
This is SO interesting. Thanks for including the references.
“I have always had this question in the back of my mind... are there two types of PA/AIG? One where the Parietal Cells are not attacked but left untouched? But rather only the intrinsic factor binding protein is destroyed or the Ileal receptor is inhibited by the IFAB. “
I’ve been wondering this too. I’ve also been trying to work out if you can have antibody parietal cell destruction over many years without your IF ever being attacked directly. I.e. b12 problems just arising from hardly any IF being produced.
This may sound like an obvious question, but do you know why we can’t measure IF itself and replace the IF (like I get prescribed thyroxine when the thyroid doesn’t produce it)?
I recently have found several oral B12 supplements that purport to be B12 with Intrinsic Factor. I know nothing about these products but have started some research to see if they are of actual use. I am always a bit wary of commercial statements on product efficacy. But it seems they may be heading in the direction that you suggest.
That’s fascinating, thank you. I will look up the info about the 2 different labs I used for previous tests and know to check for any pre-test instructions with the lab for future tests.
I note that some sources discuss two different types of Intrinsic Factor antibody - binding and blocking. I suspect we need to be clear which we are discussing!
There are two types of Intrinsic Factor Antibodies. Type 1 (Intrinsic Factor blocking antibodies) which, blocks the binding site on intrinsic factor for Vitamin B12 and type 2 (Intrinsic Factor binding antibodies) which, target a different site on intrinsic factor and prevent the intrinsic factor-Vitamin B12 complex from attaching to the binding sites in the small intestine.
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But that's what I mean - if I hadn't started SI 6 years ago, i would literally be dead by now. Without ever have gotten a positive IFAB test lol.
B12 tested whilst on injections 
MMA results - supplements or further test?
Wahey my test results are in!
Active B12 test results
