The antinuclear antibody is one of the worst tests in the history of all humanity. It is my constant companion. Why… I’ll get to that.
First, a little background. What exactly is an antinuclear antibody, also known as an ANA? In simple terms, an ANA is an antibody that is directed towards or attacks the nucleus of a cell.
How is an ANA measured?
The ANA is calculated by taking a standardized cell from the lab and mixing it with a person’s blood. If a person has antinuclear antibodies, these will stick to the standardized cells’ nuclei. At this point, there’s no way for us to know whether this has happened, so the lab tech adds fluoresceinated antibodies to the mix. These antibodies bind to ANAs that stuck to a nucleus. With the help of a specialized microscope, the lab tech can now visualize the ANA because the fluoresceinated antibodies make them light up like a Christmas tree.
My doctor told me my ANA was high. What does that mean?
Unfortunately, the tech cannot count how many ANAs they see. Instead, they see how much they can dilute the person’s blood and still see the fluoresceinated antibodies. So when you see and ANA of 1:80, that means the tech really wasn’t able to dilute very much. This is a low level. If you see a value of 1:640, that means they were able to dilute way more. This is a higher level.
What is considered a positive ANA? That answer really depends on the lab. Every lab has different cut off values, but in general, an ANA of 1:80 is typically considered positive. Whether it is clinically significant, is a whole different question. This is where the art of medicine comes into play. But before that, let’s talk about patterns because those are important too.
So let’s take an example. Your doctor runs an ANA and it comes back as 1:320 speckled pattern. So what does that mean? When the lab tech was looking at the fluoresceinated antibodies, it basically literally looked speckled. There are many other kinds of patterns: homogenous, centromere, nucleolar, speckled, rim etc. Each of these patterns are associated with a set of specific nuclear antibodies. For example, the speckled pattern is associated with SSA, SSB, RNP, Smith, and Ku antibodies. These specific nuclear antibodies are themselves associated with specific autoimmune diseases. It’s important to take ANA patterns with a grain of salt because interpretation highly depends on the experience of the lab tech.
I’m not going to go more into details regarding specific nuclear antibodies because first, there’s about 150 of them and second, they’re all associated with different diseases lupus being one of them. That’s a lot of material to cover in one article.
When is an ANA clinically significant?
Now that we understand what an ANA actually is, we can now start to approach the subject of clinical significance AND when it is appropriate to test someone for it.
The problem with the ANA is that it can be found in normal healthy people.
- ANA 1:40 is found in 20 – 30% of healthy people
- ANA 1:80 is found in 10 – 15% of healthy people
- ANA 1:160 is found in 5% of healthy people
- ANA 1:320 is found in 3% of healthy people
- ANA can be positive in 5 – 25% of healthy people with a family member suffering from lupus
- ANA can be positive in up to 70% of people aged above 70 years
To complicate things even more, an ANA can be present in someone that is about to develop an autoimmune disease… UP TO 10 YEARS before they actually develop the disease. It can be positive in people suffering from cancer, people suffering from infections like tuberculosis, HIV, hepatitis C, mononucleosis etc. It can even be positive when people are taking certain medications. Not terribly not helpful right?
So someone runs an ANA just because and it’s positive.
- Does it mean anything?
- Is the person one of those healthy normal individuals that has a positive ANA?
- Is the person going to develop an autoimmune disease in the future?
In this scenario, I would say that this test is of low clinical significance because it was obtained without purpose. Because so many people that are completely healthy have an ANA, the test should only be run if a person is manifesting a symptom or better yet, multiple symptoms that are suggestive of an autoimmune disease like lupus, Sjögren’s syndrome, systemic sclerosis, mixed connective tissue disease, etc. In that situation, it is helping answer a question.
If you’ve read my previous post, 8 important warning signs of scleroderma, you’ll remember that Raynaud’s phenomenon is an important red flag for scleroderma. The vast majority of people suffering from Raynaud’s has no underlying autoimmune disease. A small proportion does. This is the perfect scenario, where an ANA would be useful. If the ANA is negative, the person likely will NOT develop an autoimmune disease. If the ANA is positive, then the person it at high risk of developing an autoimmune disease like scleroderma. This person should be monitored more closely and probably have some follow-up blood tests.
Let’s wrap things up
Ultimately it all boils down to this simple fact: doctors treat people not numbers.
As a physician I care about symptoms and signs way more than unreliable lab tests. Don’t get me wrong, these tests are important. For example, over 99% of people suffering from systemic lupus erythematosus have a positive ANA. It’s pretty much safe to say that if someone tests negative for ANA, they likely don’t have lupus. FYI that other less than 1% usually has a positive SSA, they have a problem with their complement system, or they have a lot of protein in their urine (nephrotic syndrome).
I hope I’ve helped you better understand the elusive and mysterious ANA. Again, this information does not constitute medical advice. If you’ve tested positive for an ANA and have more questions, I highly encourage you to speak with your physician or local rheumatologist. And remember, symptoms, symptoms, symptoms.
Rheumatology Secrets 3rd edition