Do You Have Antibodies?

Understanding Sjogren's antibodies (autoantibodies)

“Seronegative Sjogren’s” is the official term used for Sjogren's patients who test negative for SSA (SSA-negative). Conversely, seropositive patients test positive for SSA (SSA-positive). NOTE: SSA is widely used as a shorthand term meaning "anti-SSA autoantibodies".

However some rheumatologists don't stick to this convention, and may consider other common autoantibodies found in Sjogren’s such as ANA, SSB, RF, as "seropositive" Sjogren's. This can be confusing, so it is a good idea to clarify what your doctor means when they use the terms "seropositive" or "seronegative".

SSA and SSB are also known as “Sjogren’s antibodies”. This term is misleading because both SSA and SSB can be found in other diseases such as lupus and systemic sclerosis. About 10% of the healthy population will be positive SSA and/or SSB (166). You can still have Sjogren's even when all your blood tests are normal. Antibody tests are CLUES to diagnosis not a yes-or-no test. A positive SSA does not mean you "tested positive for Sjogren's". Sjogren's diagnosis considers many factors, including, but not limited, to blood tests, including SSA. See the Glossary and Labs for Diagnosis to learn more about tests used for diagnosis.

Seronegative (SSA-negative) 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's commonly reported that 30% (one in three) of people with Sjogren's are seronegative, the actual number is likely much higher because the lack of a positive blood test often makes it harder to get a diagnosis.

See SSA AND SJOGREN'S and to learn why overemphasizing SSA leaves many people with Sjogren's undiagnosed. For more self-advocacy tools, see MYTHS ABOUT SJOGREN'S and MYTHS ABOUT DIAGNOSIS.

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

Everyone with Sjogren’s, including SSA-negative patients, should be routinely monitored for systemic (non-dryness) 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, including SSA-negative patients, can be found to have at least one (38, 61).

Some rheumatologists believe, incorrectly, that seronegative patients don’t get systemic manifestations. In fact, SSA-negative patients have the potential to develop almost every systemic manifestation that SSA-positive patients do (139) and are even more likely to have gastrointestinal (112) and neurologic manifestations, especially autonomic disorders and small fiber neuropathy (SFN) (161, 175, 184). These systemic features often become symptomatic before sicca (dryness) appears.

SSA-negative Sjogren's patients often experience higher levels of fatigue, cognitive problems ("brain fog"), and muscle pain. These symptoms are a top patient concern, yet often remain unaddressed by clinicians (161). They are core systemic features of the disease but frequently psychologized or misattributed to fibromyalgia (113). Learn why the "fibromyalgia" label should be dropped once people are diagnosed with Sjogren's.

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

SSA-positive patients are more likely to develop lymphoma and organ involvement, but these may also occur in seronegative patients. Seropositive patients have higher rates of vasculitis (113).

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 seronegative, with patients having neither SSA nor SSB (192). The Sjogren’s Pulmonary Clinical Practice Guidelines emphasize that all patients should be screened for lung disease, regardless of antibody status.

SSA is not an independent risk factor for increased mortality in Sjogren's. Data from a large registry called the Sjogren's Big Data Consortium shows that cryoglobulins and the ESSDAI*, but not SSA, are independently associated increased mortality rate in Sjogren's, which is about twice that in the general population (254). This means that SSA is not appropriate to use as a prognostic indicator. * This page explains the ESSDAI, the EULAR Sjogren's Syndrome Disease Activity Index.

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

Self-Advocacy tools: What to do if your clinician downplays seronegative Sjogren’s

You may need to counter the misconception that SSA-negative patients don't get 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. Lung disease is a serious systemic manifestation that occurs in SSA positive and negative Sjogren's. Because lung disease is so common (and underdiagnosed) in Sjogren’s, the information below reinforces that seronegative patients are at risk for developing serious systemic complications. Copy this article by Chen et al and highlight the conclusion in the abstract. This retrospective study found that patients negative for SSA and SSB were at higher risk of interstitial lung disease (ILD). This is just one study; others studies point to anti-Ro-52, a subtype of SSA, as associated with ILD. Still, it is clear that seronegative Sjogren's are at risk for ILD and other types of lung disease and should be monitored accordingly. Learn more about Sjogren's lung disease here.

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)., and the blog post, GASTROINTESTINAL(GI) MANIFESTATIONS. 4. If you have neurological features that are not being taken seriously, consider sharing one of these resources. Each of these articles is free to print (open access).

• This short summary of SFN in Sjogren's, noting delayed diagnosis when neuropathy precedes sicca, and the tendency to more often impact patients who do not have SSA or SSB.
  

• Print Small Fiber Neuropathy for the Rheumatologist from the January, 2024 issue of the American College of Rheumatology newsletter, The Rheumatologist. Highlight these sentences (found in the Evaluation section):

  "Patients with small fiber neuropathy and Sjögren’s are more commonly seronegative and, thus, lack anti-SSA and anti-SSB autoantibodies."
  

• Kathy Hammitt’s article about the patient perspective (161) Click the orange box that says "Free to View" on the page to access the PDF.
  

• This review article about neurologic manifestations in Sjogren’s (175), noting that it fails to adequately address autonomic disorders.
  

• This article by Segal et al: You can highlight these sentences in the abstract: "Chronic pain is pervasive in both seropositive and seronegative primary SS patients, while pain severity and functional impairment are greater in seronegative patients. Neuropathic pain is equally prevalent and is the predominant pain phenotype in patients with moderate to severe pain." (my bolds)
  

• This excellent review article about Small fiber neuropathy (SFN), includes Sjogren’s in the discussion, with some mention of autonomic aspects and “fibromyalgia” as SFN (184).
  

Please note: Most clinicians are not familiar with the autonomic disorders and do not know about their high prevalence in Sjogren’s.

We are all in the same boat!