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ICYMI: Autoantibodies Anonymous

akavanaugh@ucsd.edu
Jul 03, 2026 8:00 am

Editor's note: This blog originally appeared March 24, 2026, and is being shared this week as part of our In Case You Missed It (ICYMI) series. Enjoy!

At first, it seemed similar to many other such sessions – a circle of folding chairs, a group of colleagues whose visages exuded understanding and acceptance – but this was special. I started the meeting…. “Hi, my name is Artie,”

“Hi Artie” came the reply from the group, synchronous and warm.

“It has been 1 year since I last ordered a myositis panel!” I announced, nervously. But the loud applause and earnest congratulations were quite encouraging. After all, it is not easy being an autoantibody nihilist these days. While most will admit that the use of autoantibody testing has gotten out of hand in rheumatology, the pressure to “… just check another antibody panel” is intense. Pressure comes both from patients as well as colleagues. The response of my peers assured me I had made a good choice.

I track my disillusionment with testing back to residency days. In the spirited competition between Internal Medicine and Surgery, it was natural to create nicknames. Among other monikers, our surgical colleagues derisively called internists “hummers”. I asked a surgical resident friend what that meant…  she said, “you internists order all these fancy tests… then when you get the results, you go ‘hmmmmm’…. but you don’t do anything!”. Ouch! If that is true, then rheumatologists may be the biggest hummers of all!

It is a challenge to be against autoantibodies, as they have such a storied place in rheumatology. The discovery of the antinuclear antibody (ANA) helped change SLE from a mysterious condition best diagnosed at autopsy, to a systemic autoimmune disease for we have learned a tremendous amount. The discovery of Rheumatoid Factor (RF) helped spur research and developments in Rheumatoid Arthritis (RA). Autoantibodies can help define disease activity and severity and domain involvement in a number of diverse rheumatologic conditions: some are even etiologically relevant.

But several things have happened over the years. The number of autoantibody tests has expanded tremendously. It is hard to keep up with the panoply of available tests, let alone their potential utility in the clinic. Also, techniques for performing autoantibody tests have evolved. In the old days, the techniques generally required high concentrations of high affinity antibodies (remember the Farr assay? Crithidia lucillae? Ouchterlony plates?) for a positive result. As a result, the tests tended to be very specific, but not completely sensitive. Remember how we taught our primary care colleagues that “a positive anti-Smith antibody or anti-dsDNA antibody meant that the patient had lupus”? But now the tests are done mostly by ELISA; much more sensitive, but much less specific. How many referrals do we get for a chronic pain patient with an ANA of 1:40 and a dsDNA of 4.01 (where <4 is negative, but a strong positive is > 20)?  Hmmmmm….

Maybe most importantly, how autoantibody tests are used has changed. I call it “when good tests go bad”. When ANCA testing was new, it was incredibly useful. The reason was that it was only ordered in patients with a reasonably high pre-test probability of having vasculitis. Now, it is obtained for patients whose clinical picture bears no semblance to vasculitis. It is ordered as a “rule out vasculitis.”. When ordered in clinical circumstances with a very low pre-test probability of vasculitis, the test is much less useful. Professor Tom Huizinga of the Netherlands, tells a story about the early days of CCP testing. He appeared on Dutch television and proclaimed the CCP test was “very specific for Rheumatoid Arthritis”. For years after, his clinic was full of CCP+ fibromyalgia patients!

What is the downside of poor autoantibody testing? Cost, for one. While individual testing may be only hundreds of dollars, if there is no clinical utility, that is completely wasted. Worse, spurious positive results often engender additional testing, which involves additional costs, anxious patients, and wasted time for rheumatologists.

So, the next time you are tempted to order a “scleroderma panel” or a “myositis panel”; please stop and think. Make sure that the results will be impactful. Last year a young trainee in the clinic saw a new patient with scleroderma. Asked what they wanted to do, they replied “I want to check an Scl-70”. I asked why, and they replied, “because it is associated with interstitial lung disease in scleroderma patients”. A correct statement, and it showed the trainee had done their reading! The only problem was that the patient had come to us from Pulmonary clinic! With a diagnosis of ILD, having had an extensive workup! So, when the results of the Scl-70 or ‘scleroderma panel’ came back…positive or negative… what would we say? Hmmmmm……

Better yet.. start a chapter of ‘Autoantibodies Anonymous’ for your local rheumatologists! I will give out the ‘1 year chip’ gladly to all who make it!

Join The Discussion

leonard h calabrese

| Jul 04, 2026 1:04 pm

Artie- couldn’t agree more- laboratory tests must be subjected to. Baysean reasoning as you note- the myositis panel is an excellent example where bye and large should be reserved to be ordered after myositis has been diagnosed or at least highly suspected (hi pretest probability ) where it can then provide data that allows clinical subset, identification which can have profound implications for prognosis and management. ( probability of malignancy, ILD, treatment, selection, etc..). Well said.
Lenny

Raina Pelofsky

| Jul 04, 2026 3:30 pm

As I mentioned when this article first came out, it's important to be guided by the antibody testing included in the current classification criteria for whichever diagnosis you're considering. SLE, for example. Although antiphospholipid antibodies (aPL) are part of the 2019 EULAR/ACR classification criteria for SLE, Munawar & Sherazi found that only 15% of SLE patients are ever tested. Why?? The utility of aPL testing is well established, especially in late-onset disease: 1) Patients may require the 2 points conferred by aPL to reach the threshold for SLE classification/diagnosis; 2) All patients with a definitive SLE diagnosis require aPL testing for accurate cardiovascular risk stratification, regardless of whether they have a history of thrombosis or pregnancy complications. In this example, patients positive for aPL should be counseled regarding their additional risks, and shared decision-making as to appropriate prophylactic treatment should occur. Bottom line: Order the antibody testing included in the CURRENT classification criteria for the disease. Not doing so could lead to diagnostic delay or failure, and/or high-risk phenotypes could go unrecognized.

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Disclosures
The author has no conflicts of interest to disclose related to this subject
Artie Kavanaugh, MD (20 Posts)

Dr. Arthur Kavanaugh is Professor of Medicine at the University of California, San Diego School of Medicine. In addition, he is the Director of the Center for Innovative Therapy in the UCSD Division of Rheumatology, Allergy, and Immunology. Dr Kavanaugh has authored more than 500 publications. He is on the editorial board for several journals, and has served as peer reviewer for many scientific journals. Dr Kavanaugh’s main research interest is in clinical research, particularly translational aspects of rheumatology research. This has included work delineating the pathophysiology of rheumatic diseases as well as defining changes associated with novel immunomodulatory therapies. The focus of many clinical projects has been RA and psoriatic arthritis, but Dr Kavanaugh has conducted many studies in other autoimmune conditions, including SLE, ankylosing spondylitis, inflammatory bowel disease, and others. In addition, he has performed studies focusing on novel imaging methods and also clinical outcomes. 

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