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ANAs in the Lupus Puzzle


ANAs in the Lupus Puzzle
By A. G. Moore 5/14/2013

Immunofluorescence Pattern of Double Stranded DNA Antibodies
By Simon Caulton
On Wikimedia Commons

What’s going on?” I asked my doctor. It was 1992. The acute phase of a viral infection had subsided but several symptoms persisted. Joints in my hand were swollen; my blood pressure was elevated; my thighs and my feet ached.

The doctor examined me, asked questions and drew blood. He had likely formed an idea about what might be “going on”; the blood test would give him more clues. When the lab report came back, he learned something about the direction his inquiry should take: I had tested positive for antinuclear antibodies (ANAs). This result was a sign, not an answer. In order to get an answer, he told me, I needed to see a rheumatologist.

Back then, in 1992, I didn’t know what a positive ANA lab report meant. Over time, though, I  learned a great deal about this laboratory test. For one thing, I discovered that the term antinuclear antibodies embraces a lot of different kinds of autoantibodies. Autoantibodies are at the heart of autoimmune disease.They are like rogue cells and attack the very organism that has given rise to them.

After a laboratory sends back a positive ANA finding, the doctor has a range of options: if the patient is asymptomatic (has no other signs of disease), the doctor is likely to file the lab report away and do nothing because positive ANA tests are found in about 5% of apparently healthy people.

Another option a doctor has, if the patient is symptomatic, is to draw blood and send the sample back to the lab for more definitive testing. In my case, the rheumatologist to whom I’d been referred looked for specific antinuclear antibodies. Lupus, at this point, was a distinct possibility. If my second set of lab tests came back positive for particular antibodies, such as anti-double stranded DNA or anti-Smith, then the doctor would have a clearer idea about what he was dealing with. These two antinuclear antiboidies are rarely found in a patient who does not have lupus.

Since that first daymore than 20 years ago–when a doctor told me my blood had tested positive for antinuclear antibodies, I‘ve learned:

*  While a positive ANA may indicate an autoimmune disease is present, a negative doesn’t eliminate the possibility. Research shows that about 3% of the people who have lupus are “sero-negative”–that is, they get a negative ANA lab result. In a way, this is unfortunate, because it is so widely believed that ANA is a threshold test for lupus that precious time may be lost as doctors look elsewhere for an answer to a patient’s complaints. Or, worse yet, doctors may stop looking for an answer altogether.

*  As lab results come in and a patient tests positive for specific kinds of antinuclear antibodies, doctors may discover exactly what’s going on. Certain antinuclear antibodies are associated with specific symptoms: anti double stranded DNA, for example, appears often in lupus patients who have kidney involvement . Anti-Ro is found, often, in patients with cutaneous lupus (SCLE). Anti-Ro is also often present in the blood of patients who have both Sogren’s Syndrome and systemic lupus.

*  ANAs are found not only in autoimmune diseases but also in certain cancers. Pelvic and breast cancers, for example, may trigger a positive ANA. And, it seems that ANAs are found in blood samples at increasing rates as people grow older–this finding is not associated with any evident disease process. In one study, 79% of people over the age of 100 had elevated levels of at least one kind of autoantibody.

The most interesting thing I learned about antinuclear antibodies is that, while they can be extremely helpful diagnostically, they are in many ways a mystery. Some researchers question whether they are merely bystanders in the disease process or whether they are themselves precipitators of disease. An article in the Journal of Rheumatology asks just that question.  It looks at the role of autoantibodies in the development of atherosclerosis and age-related immune system decline.

“What is going on?” That was the question with which I began this post. It’s the question on the mind of every doctor when a worried patient arrives at the office. Doctors have many tools to help them find the answer to this question. The test for antinuclear antibodies is one of the tools. However, this test is never by itself an answer–it just allows doctors to ask more pointed questions.

I didn’t know any of this in 1992 when I learned a laboratory detected antinuclear antibodies in my blood. If my understanding of this test had been better, I might have been more patient as the doctor searched for answers. I might not have been so unsettled by his reticence. How could he tell me what he did not know? He was on the path to discovery and we would both have to wait until information was more definitive.

Lupus is a perplexing disease to diagnose and challenging disease to treat. If the patient understands some of the difficulties, such as what an ANA test can and cannot reveal, then cooperation with the doctor and productive collaboration is more likely to take place.


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