I believe AMA has 9 different codes with M2 suggesting pbc. Connective tissue can possibly indicate schleroderma. There may be more connective tissues conditions I am not aware of. 🦋
Antimitochondrial antibodies (AMAs) are detectable by indirect immunofluorescence in >90% of patients with primary biliary cirrhosis (PBC), but this method also detects AMAs of differing specificities in other diseases. The mitochondrial antigens recognized by AMAs in patients' sera have been classified numerically as M1 through M9, with the M2 antigen complex recognized by AMAs in sera from patients with PBC. M2 antigen is comprised of enzyme proteins of the 2-oxoacid dehydrogenase complex that are located on inner mitochondrial membranes. Included in this group of autoantigens are the pyruvate dehydrogenase complex, and 2-oxoglutarate dehydrogenase complex.
Reference Values
Negative: <0.1 Units
Borderline: 0.1-0.3 Units
Weakly positive: 0.4-0.9 Units
Positive: > or =1.0 Units
Reference values apply to all ages.
Interpretation
Positive results for antimitochondrial antibody (AMA) of M2 specificity are highly specific for primary biliary cirrhosis (PBC), and false-negative results are rare.
A positive result for AMA of M2 specificity in a patient with clinical features of PBC is virtually diagnostic for this disease.
It is incorrect to say that a positive result of AMA-M2 is virtually diagnostic for PBC.
Yes AMA-M2 can be strongly indicative of PBC, but absolutely no diagnosis of PBC can be made on AMA alone: - or by reference to any one diagnostic criteria alone.
2 out of 3 diagnostic criteria, for PBC, must always be met for a diagnosis of PBC: that is:
- AMAs and/or:
- Abnormal liver function tests (LFTS) typical of PBC (& other bloods) and/or:
- a liver biopsy that shows damage to the microscopic biliary tubules of the liver (although fibroscans instead of biopsies, are increasingly accepted, from what I have read on here).
2 out of 3 of these diagnostic criteria have to be met, for a formal/official diagnosis of PBC.
NB in the UK 'Blood Donor' statistics show that 10% of the population carry AMAs, but only about 1.5 - 2.00% of those people go on to develop PBC.
Symptoms can help to guide the tests that should be followed, but symptoms alone are not enough for a diagnosis of PBC. There are many complex autoimmune conditions, and in cases of uncertain diagnosis, extensive testing, over a period of time, must be done to rule out all other autoimmune conditions.
Nb I have AMA-M2, in high levels (the level is not supposed to be indicative of a diagnosis): some people just have AMAs. They were first noted, in me, in 1992 and I am tested every year, with extra checks if ever there have been concerns, and I am still perfectly healthy and don't have PBC. I saw one of the most respected UK PBC consultants a few years ago, when a new-to-me consultant wanted to diagnose me as PBC. The expert said - after much more testing, and checking of family history etc - that, 'no, I did not have PBC,' and that it is inadvisable to give Urso etc, if PBC is not formally present.
Hi Gritty Reads, thank you for such great information. I have a question for you... My AMA came back negative, but my AMA M2 is positive. All other blood tests are totally normal except mildly elevated LFT. So does that mean I have PBC? Or could it be something else. One doctor said it could be NASH because sometimes a positive M2 is present in Nash. But I'm having a hard time thinking that is correct. Or do you think I could be in early stages of PBC?
Obviously I'm not an expert, and as I don't actually have PBC I hesitate to comment on issues that are outside my main area of concern (which is people being diagnosed as having PBC, when they only have AMA-M2 - as having just one of the 3 diagnostic criteria is not enough to diagnose someone with PBC, although they should continue to be monitored every year).
So, I don't know much about NASH, and cannot comment on that.
However, I don't understand what you mean when you say that your "AMA came back negative but my AMA M2 is positive."
Were these from 2 separates sets of tests? That might explain it. Or, should the AMA be 'ANA'? which is something altogether different.
I think you should talk to the advisors at the 'PBC Foundation' : a UK - based advice and support group for PBC sufferers. They host this site on Health Unlocked, and there is a link to their website at the top of the page - or Google 'PBC foundation' - where you will find email and phone contact details. Also the site is a mine of info and if you join (it's free) you get much more access.
My understanding is as follows: first there are about 9 sub-types of AMA (nb: AMA means 'antimitochondrial antibodies'). AMA-M2 is the subtype linked to PBC, and its presence in amounts over a certain level is a strong indicator of PBC. However, my understanding is that AMAs can be present in very, very small amounts, and these very low levels are generally ignored. In people who possibly have PBC, the levels of AMA-M2 are much higher, and this is when alarm bells should ring with any Medic, to do more tests.
As you say that your lfts were elevated, if you also have high AMAs, then the lfts are another diagnostic feature for PBC.
However, there are several different chemicals that can be high in lft tests, and any confusion over diagnosis could depend which ones are raised in your case. The usual suspects in PBC are ALP, ALT, AST, although my own specialist also likes to keep an eye on GGT levels (not strictly an lft chemical).
My understanding is that you should continue to have lfts tested over a 6 month period to see what happens, as well as testing for all other liver and autoimmune conditions. It is a complicated area, so it helps to see an experienced Heptologist, and particularly one who is a PBC specialist, if possible. I hope this helsp a bit, but please do talk to the 'PBC Foundation' people.
Thank you so much for your information, it helps me to understand all this crazy stuff.
The one blood test was an AMA titer serum which was negitive. The other was the M2 test that was positive. I'm really confused too. I hope to see a doctor soon.thsnk you again for help!
OK makes sense so is Ana - m2, just really ama group
AMA - M2 is one of a group of 9. Is your report saying Ana or is your spelling check altering what you type in. As ANA is a different antibody I believe.
I agree with GrittyReads you need to speak to your doctor about the results. Ana does have sub groups however I don’t know how they are communicated in lab reports or what that would suggest in your case as it would depend on the levels and other factors. Just as it would with AMA. I just remember having the test very early on in my autoimmune journey with PBC. Let us know how you get on.
I think you need to check what he means. ANA is something different, though I don't know if there even is an 'ANA M2'. I would talk to the advisors at the 'PBC Foundation' (follow links to their website, above), they are wonderful and the 'PBC F' website is amazing. Hope this helps.
OK I had a liver biopsy that diagnosed pbc, but keep being tested for other things due to joint pain, it was just that I noticed in in gastroenterology report probably a type error
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