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LAB TESTS THAT SUPPORT
A SJOGREN'S DIAGNOSIS

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Key Concepts

Be sure to read the Introduction to Diagnosis to better understand this page.


No single test diagnoses Sjogren’s. Sjogren’s is a clinical diagnosis that is supported by, but cannot be ruled out by, diagnostic tests. 

 

Sjogren’s is a distinct disease. Manifestations and blood test results may overlap with other autoimmune rheumatic diseases (AIRDs) such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). 

See the Myths About Diagnosis page to learn more about common myths that get in the way of diagnosis.  

Note: This page discusses laboratory tests in the context of diagnosis. There are many other tests that are used for ongoing monitoring and care. 

Initial Sjogren's Labs
  • ANA, SSA, SSB, CCP, RF, ESR, CRP (titers do not reflect disease severity)    

  •  CBC with differential and platelets, serum potassium, LFTs

  •  UA, Random urine protein/Cr

  •  HIV, HEP C       

  •  If SSA negative, minor salivary gland biopsy (MSGB), usually via rheumatology consult.

Note:  These initial tests are commonly used for Sjogren's diagnosis, with additional tests considered as indicated. 

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Individual Labs Used For Diagnosis

Many of the tests used to support a Sjogren's diagnosis are part of the Sjogren's classification criteria. Many people who do have Sjogren's do not fulfill the classification criteria.

The "lip biopsy" aka minor salivary gland biopsy (MSGB) 

The lip biopsy (MSGB) is an important part of the Sjogren's classification criteria, but it is not always positive in people with Sjogren's.  See Myth #5 on the MYTHS ABOUT DIAGNOSIS page. 

 

SSA (anti-Ro antibodies)
The SSA is the most helpful blood test used to support a diagnosis of Sjogren's. However, 30-40% of people with Sjogren's do not have a positive SSA. SSA is also seen in other AIRDs, especially SLE, and sometimes in healthy people (5, 6, 9). 
See Myth #2 on the MYTHS ABOUT DIAGNOSIS page and SSA and Sjogren's to learn why this SSA is often negative in people with Sjogren's. 

SSB (anti-La)
SSB is present in about 40% of Sjogren’s patients. Like SSA, SSB may be seen in other autoimmune rheumatic diseases, especially SLE, and sometimes in healthy people (4, 5, 6, 9)Rheumatologists often like to see the SSB test prior to referral because of its association it may be associated with organ involvement and certain cardiac arrhythmias.  
SSB is usually (with exceptions) present only when SSA is present. For that reason, SSB is no longer used in the Sjogren's
classification criteria. SSB without SSA may still support a Sjogren's diagnosis.  See Myth # 3 on the MYTHS ABOUT DIAGNOSIS page.

SSB and SSA are types of ANA. 
Still, 
10% of Sjogren's patients with SSA have a negative ANA test and people with suspected Sjogren's should be tested for ANA, often using the ENA panel. 

SSA intro
What is the ANA panel?
 

"The ANA test evaluates the presence or absence of autoantibodies, while the ENA panel aims to determine to what proteins in the cell nucleus the autoantibodies recognize. If an ANA test is negative, then the person is extremely unlikely to test positive for a specific antinuclear antibody (which is what the ENA panel tests). In Sjogren's, SSA sometimes occurs without a positive ANA."

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ANA (Anti-Nuclear Antibodies) -  Positive in 50-80 % of  Sjogren’s. ANA is positive in many other autoimmune rheumatic diseases (5, 6, 9).  Some healthy people carry ANA, although usually at lower titers such as 1:80 or 1:160 (6). Infections, liver disease, and other conditions may also be associated with a positive ANA test. Higher titers are more likely to be associated with autoimmunity but may be caused by other conditions such as infections, malignancies (cancer) or certain medications.
 
Learn more about ANA tests here.

 

CCP (anti-citrullinated peptide, a subset of ACPA, anti-citrullinated protein antibodies)
Positive antibodies to CCP in the presence of erosive arthritis suggests s suggestive of RA. However, these autoantibodies may be occasionally seen in Sjogren’s (3-10%) (5, 11), SLE, and other AIRDs. A rheumatologist’s expertise is needed for interpreting this test when a patient presents CCP/ACPA along with clinical signs and symptoms of Sjogren’s. Sjogren's can cause inflammatory arthritis (201).  

RF (Rheumatoid factor) 
RF is positive in many AIRDs and in 60-70% of Sjogren’s patients. Also positive in many infections, and occasionally in healthy people (6). 

CRP and ESR 

These classic markers of inflammation are often completely normal in Sjogren's, even though Sjogren's is a systemic inflammatory disease. Inflammation can be detected by other inflammatory markers in Sjogren's but these are not standard tests that are readily available in the clinic setting. 
Learn more here: 
Sjogren's and Inflammation Part I
Sjogren's and Inflammation, Part II

 

Completed blood count (CBC) with differential and platelets
Cytopenia refers to low counts of various blood cell types. 30-60% of Sjogren's patients have one or more types of cytopenia (151, Ch. 6).
Cytopenia is a systemic feature of Sjogren's. It is one of the 12 major categories of the  twelve categories in the ESSDAI, a research tool used to measure systemic activity.
Most cytopenia is mild and asymptomatic. Cytopenia can sometimes be caused by medications. 

 

TYPES OF CYTOPENIA
  • Low white blood cells (lymphopenia and neutropenia)

  • Low platelets (thrombocytopenia)

  • Low red blood cells (anemia)


The type of anemia caused by Sjogren's is called anemia of chronic disease. It is not the same as iron deficiency anemia, although the two may occur together. Severe thrombocytopenia or autoimmune hemolytic anemia are uncommon but serious complications that require e management by a hematologist (10).

Serum Potassium - Hypokalemia (low serum potassium) may indicate Sjogren's kidney disease (10).

UA, random urine protein and creatinine - Mild proteinuria (protein in the urine) is common in Sjogren’s, but usually occurs without symptoms. Learn more about Sjogren's and kidney disease. 

Liver tests (often inaccurately called liver function tests, or LFTs) - May indicate liver and/or biliary tract disease. Learn more about Liver Disease and Sjogren's. 

HIV/ Hepatitis C - These infections have many symptoms that overlap with Sjogren’s, such as sicca and flu-like fatigue. It is important to rule these out early on.

More about autoantibody tests

How do autoantibodies help diagnose Sjogren’s and other autoimmune diseases?

Autoantibodies help clinicians distinguish between autoimmune diseases that have overlapping manifestations. The relationship between autoantibodies and various diseases can be complicated. Many autoantibodies, including SSA, are associated with several diseases. There is no one "Sjogren's test" or "lupus test". 
For more information, see So What is Sjogren's, Really? 

What exactly are “Sjogren’s antibodies”?   

SSA (anti-Ro) and SSB (anti-La) are known as Sjogren’s antibodies. This terminology is inaccurate because SSA and SSB are also seen in other autoimmune rheumatic diseases, especially SLE. 
 

Among Sjogren's researchers and experts, the term “seropositive” usually refers to patients who are positive for SSA. Some researchers and rheumatologists may include ANA, SSB, or RF along with SSA in their definition of seropositivity. Many primary care providers equate seropositive with positive RF. Inconsistent terminology can be very confusing.

SSA,ANA

SSA and ANA titers do not reflect disease activity or severity (6, 165).

ANA and SSA do not tell you how sick you are. They should not be used to guide monitoring and treatment decisions.  Every Sjogren's patient, regardless of symptoms or antibody status, should be monitored for a wide variety of systemic manifestations.  
Learn more about What is Good Sjogren's Care?

"In a patient who has Sjögren’s syndrome with SSA (Ro) and/or SSB (La) antibodies, the levels of these antibodies do not correlate with disease activity. In fact, these levels remain fairly constant in a given patient."  ~ Alan Baer, MD, October 2012 The Moisture Seekers

Should SSA and ANA tests be used to follow the disease?

No. With rare exceptions, these tests should usually not be repeated once they are positive.  It my be useful to repeat SSA and ANA if the initial result was borderline(e.g., low titers), or as part of a research study.
See this article to learn why repeat testing is not generally recommended.

Other tests that can support a Sjogren's diagnosis

There are many other tests that can help point to a Sjogren’s diagnosis. Blood tests showing cytopenia and hypergammaglobulinemia (elevated IgG) are common in Sjogren’s. Low complement levels may also point to a Sjogren's (or SLE) diagnosis. These tests are part of the big clinical picture, beyond the classification criteria, that can help point to Sjogren’s diagnosis (3). 

Salivary Gland Ultrasound (SGUS) may eventually be added to the classification criteria, or even replace the lip biopsy (MSGB). Like the lip biopsy, SGUS focuses on salivary gland damage, which may exclude early presentations and people with systemic presentations who do have Sjogren's.  
See Myth # 6 on the MYTHS ABOUT DIAGNOSIS page. 

"Early Sjogren's antibodies"

New biomarkers are being investigated, including PSP (parotid secretory protein), CA-6 (carbonic anhydrase VI), various tear proteins (9, 15) and others.
Because these tests appear to high numbers of false positive tests, they are not widely accepted by rheumatologists as evidence of Sjogren's.  

Updated 04-21-2024

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