SSA, Autoimmunity, and Sjogren's

Sjogren’s is an autoimmune rheumatic disease (AIRD).

Sjogren's, an AIRD, belongs to the same family of diseases as rheumatoid arthritis (RA), lupus, and systemic sclerosis. These systemic diseases share overlapping features, comorbidities, and autoantibodies. All these diseases can cause arthritis, lung disease, and skin rashes. They are never just one thing. RA is not just a disease of the joints. Lupus is not just a butterfly rash and kidney disease. Systemic sclerosis is not just a skin disease. And Sjogren's is never just dryness (sicca).

Sjogren’s is a complex, chronic, systemic inflammatory disease, never just dryness.

While dryness impacts most people with Sjogren's, it is not a universal symptom of Sjogren's. Many doctors rely on dryness symptoms and measurements for diagnosis. This is a problem because systemic problems may be present for years before any dryness appears. For example, neurological issues such as small fiber neuropathy and dysautonomia often show up well before a patient experiences dryness. This reliance on a single symptom (dryness) leads to misdiagnosis and delays in care for many patients.

Unfortunately, doctors are still being taught that Sjogren's is mostly a dryness disease, and that most patients don't have systemic manifestations that affect the whole body. This misconception often leads to a delayed or missed diagnosis and inadequate care.     Sjogren's is a serious disease, but doctors often don't take it seriously. Read this blog post to learn why.

SSA is the main autoantibody used to diagnosed Sjogren's, but many people with Sjogren’s do not test positive for SSA.

While a large majority of patients with RA, lupus, and systemic sclerosis test positive for one or more autoantibodies that count toward diagnosis, this is not the case for Sjogren's.  At least 1 in 3 Sjogren's patients (6) do not test positive for SSA. Sjogren's is associated with a variety of autoantibodies, but SSA is overemphasized. Many rheumatologists will not diagnose Sjogren's in people who don't have SSA, even when patients have a clear clinical picture of the disease. SSA is not a "Sjogren's test". SSA is not specific to Sjogren’s. SSA is often present in other rheumatic diseases such as lupus and systemic sclerosis (166). SSA is sometimes found in people with infections such as hepatitis C and COVID-19. Some healthy people carry SSA and never develop Sjogren’s (14). Clearly, we need better tests!

Is SSA-negative Sjogren's autoimmune?

Yes. Autoimmune diseases are associated with autoantibodies. Even though SSA (with or without SSB) is the main autoantibody used for diagnosing Sjogren's, other autoantibodies such as ANA, rheumatoid factor (RF), anti-centromere antibody (ACA) are seen in Sjogren's. Many other autoantibodies have been found by researchers (153). These other autoantibodies can help support a diagnosis, but are usually not available on standard tests. Despite this, some rheumatologists refuse to diagnose or treat Sjogren's without a positive SSA, ignoring the fact that SSA-negative (seronegative) Sjogren’s is common.

What is SSA doing to your body? The short answer is, we don't know. The role of SSA and other autoantibodies in the disease process remains unclear (166). Autoantibodies serve as helpful biomarkers (indicators) for diagnosis when patients have them, but this does not mean that the autoantibodies are causing the disease. SSA does not indicate disease or severity, and SSA titers do not go up and down with disease activity (118). There is no single "root cause" for Sjogren's or other autoimmune diseases. Autoimmune diseases arise from a variety of predisposing factors and triggers. No scientist who studies the immune system would claim that these diseases have a single, simple origin. The "root cause" idea is often used by wellness influencers who want to sell you dubious products such as unproven supplements. They take advantage of desperate patients by offering simple solutions to a complex problem that they claim to understand, but don't. What drives the immune system to mistakenly attack the body is still not completely understood.

The biological processes that cause Sjogren's and other AIRDs are complex and involve many parts of the immune system. Sjogren's is a highly variable disease, as the specific pathways leading to illness can differ from patient to patient. This explains why one person with Sjogren's may have a very different experience from another. While researchers are beginning to study these distinct patient subtypes, there is still much to learn. We cannot yet predict with certainty how the disease will appear or progress in an individual. Because of this unpredictability, every patient must be monitored for a wide range of systemic manifestations.

Subtypes of Sjogren’s may involve different immune system pathways that lead to the same disease (168). More research is needed to understand the pathways that lead to Sjogren's disease, and how they may differ in different groups of patients.

HOW TO COUNTER COMMON MYTHS ABOUT SSA

• Your rheumatologist won’t diagnose you with Sjogren’s because you don’t have autoantibodies, especially SSA. Myth buster: Many people (30% or more) with Sjogren’s don’t have SSA or other typical autoantibodies such as SSB, ANA, or RF that are typically associated with Sjogren’s. Other autoantibodies may support a Sjogren's diagnosis and help guide treatment, including anti-centromere antibody (ACA). More autoantibodies are being studied to better understand their role in Sjogren's disease. See Do You Have Antibodies? and MYTHS ABOUT DIAGNOSIS for self-advocacy tools.
  

• You have had a positive blood test for SSA but a follow-up test turned negative or showed a lower titers. As a result, your rheumatologist tells you that you no longer have Sjogren’s. Myth buster: Sjogren's is a lifelong condition that does not go away. If a patient is diagnosed based on clinical features and a positive SSA antibody test, they should not have the test repeated. Changing antibody levels can be misleading and misinterpreted.
  

  Some patients are wrongly told that a decrease in their SSA titer means their disease is inactive or in remission. However, SSA titers do not reflect disease activity and should not be used to guide monitoring or treatment decisions. Similarly, patients who previously had a positive SSA test may later test negative. These patients are sometimes incorrectly told they no longer have Sjogren's. This can have serious consequences, such as the overturning of disability approval for a patient because the diagnosis was wrongly overturned. ADVOCACY TIP: If your doctor wants a follow up SSA test, ask why. There are only a few good reasons to do this (e.g., pregnancy, part of a research study) and many downsides.
  

• Your rheumatologist does not monitor or treat you for Sjogren’s because you don’t have autoantibodies such as SSA. Some clinicians incorrectly believe that Sjogren’s patients without SSA don’t develop serious systemic features. Myth buster: While SSA is a risk factor for certain complications and comorbidities, patients without SSA still have a systemic disease. Some serious outcomes are more common in SSA-positive patients, while others are more common in SSA-negative patients. Every Sjogren’s patient deserves the full range of monitoring and treatment, regardless of SSA status (139). Click here to learn more about "seropositive" vs "seronegative" Sjogren's.

Many of the medical terms on this page have been added to the Glossary. The link to the Glossary is located in the footer (the bottom) of every page.