• Sarah Schafer, MD

Do you have antibodies?

Understanding Sjogren's antibodies (autoantibodies)

“Seronegative Sjogren’s” is the official term used for patients who test negative for SS-A. Conversely, seropositive patients test positive for SS-A. Because SS-A, SS-B ANA, and RF are all common in Sjogren’s, rheumatologists sometimes choose which subset of these autoantibodies count as seropositive. This inconsistent use can be confusing. Seronegative Sjogren’s is common, comprising up to 50% of all cases (6). Some rheumatologists inappropriately refuse to diagnose Sjogren’s in people without autoantibodies. While it is common to hear that 20-30% of Sjogren’s is seronegative, the actual prevalence is likely much higher because seronegative patients are less likely to be diagnosed.

SS-A and SS-B are called “Sjogren’s antibodies”. This term is misleading because SS-A and SS-B are not unique to Sjogren’s. Like SS-A and SS-B, RF and ANA are also found in other diseases, especially rheumatoid arthritis and systemic lupus erythematosus. About 10% of the healthy population will be positive for one or more of these biomarkers (166). Please see the Glossary and the Labs for Diagnosis page to learn more about tests used for diagnosis.


Sjogren’s is a serious systemic disease, even if you don’t have antibodies.

Everyone with Sjogren’s, including seronegative patients, should be routinely monitored for systemic manifestations of the disease. This does not always happen. While most people with Sjogren’s don’t get more than a few systemic manifestations, almost every patient who is thoroughly evaluated can be found to have at least one (38,61).


Some rheumatologists believe, incorrectly, that seronegative patients don’t get systemic complications. SS-A negative patients have the potential to develop almost every systemic manifestation that SS-A positive patients do (139) and are actually more likely to have gastrointestinal (112) and neurologic manifestations (161,175,184). These systemic features often become symptomatic before sicca (dryness) appears. Seronegative patients tend to experience higher levels of fatigue, brain fog and so called “fibromyalgia” (113). These debilitating features are usually the top patient concern, yet often remain unaddressed by clinicians (161).


The only complication that appears unique to SS-A positive patients occurs during pregnancy. A small percentage of babies born to SS-A positive women develop congenital heart block and/or neonatal lupus (153). There is increasing evidence that SS-A positive patients are distinctly at risk of developing ventricular arrhythmias, but more research is needed.


SS-A positive patients appear more likely to develop lymphoma and organ involvement, but these may also occur in seronegative patients. Seropositive patients have higher rates of vasculitis (113). However, other markers (such as C3, C4, and cryoglobulins) are more accurate when assessing risk for these and other serious outcomes. See the Glossary for more information about these tests.


Lung disease appears to impact seropositive and seronegative Sjogren’s patients at similar rates. One recent study showed that 50% of Sjogren’s-associated interstitial lung disease cases were negative for both SS-A and SS-B (192). The Sjogren’s Pulmonary Clinical Practice Guidelines emphasize that patients should be screened for lung disease regardless of antibody status.

For an overview of rheumatology care, see the blog post, What is Good Sjogren’s Care?

What to do if your clinician downplays seronegative Sjogren’s or systemic manifestations

Choose one or two of the following articles to share with your clinician. Print out (or email) the entire article if it is available. Otherwise, share the abstract. Highlight key areas that you want them to see.

1. General: Because lung disease is so common (and underdiagnosed) in Sjogren’s, the information in these guidelines reinforces that seronegative patients are at risk for developing serious systemic complications. Share the Sjogren’s Pulmonary Clinical Practice Guidelines. (Every rheumatologist and PCP should have a copy) Highlight these words on the top entry of the chart on the second page “Serologic biomarkers must not be employed to evaluate for pulmonary involvement in patients with established Sjogren’s disease.”

This quote makes the point that evaluation for lung (pulmonary) involvement should be the same for all Sjogren’s patients, regardless of antibody status.

2. If you are seronegative and having trouble getting diagnosed or if your rheumatologist does not think seronegative Sjogren’s is serious, share the abstract of this article (139).

Highlight these final sentences of the abstract: “The clinical features of seronegative pSS were similar to those of seropositive pSS. The current classification criteria for pSS should not be used in the diagnosis of seronegative patients, as the agreement between the different sets of criteria was low, and some patients fell outside the classification.” 3. If your clinician insists that your gastrointestinal symptoms are not related to Sjogren’s, share the abstract of this article (112). 4. If you have neurologic features that are not being taken seriously, consider sharing one of these resources. Each of these articles is free to print (open access).



We are all in the same boat!

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