Laboratory tests that support a Sjogren's diagnosis

Key Concepts
 

  1. No one test diagnoses Sjogren’s early and accurately. Sjogren’s is a clinical diagnosis that is supported by but cannot be ruled out by diagnostic tests.
     

  2. Sjogren’s manifestations often overlap with other connective tissue diseases (CTDs). In addition, Sjogren’s may co-occur with other CTDs. Rheumatologists need to look at many factors to determine the correct diagnosis.
     

  3. Autoantibody titers and inflammatory markers do not correlate with disease activity.

Initial Sjogren's Labs

  •  ANA, SS-A, (? SS-B), CCP, RF, ESR, CRP    (titers not ~ disease severity)    

  •  CBC with diff and platelets, serum potassium, LFTs

  •  UA, Random urine protein/Cr

  •  HIV, HEP C       

  •  Minor salivary gland biopsy (MSGB)- if SS-A  negative- Usually via rheumatology consult.

Note:   I consulted with several Sjogren’s experts when I developed this list of initial labs for PCPs. These tests may vary depending on the medical institution/ rheumatologist the PCP is working with.    

Description of Individual labs used for diagnosis

MSGB (“lip biopsy)-  see separate page.  MSGB is an important part of the Classification Criteria.

 

SS-A (anti-Ro) is the blood test that is most helpful in supporting a diagnosis of Sjogren’s.  It is present in 55-70 % of Sjogren’s patients.  SS-A is seen in other CTDs, especially lupus, and sometimes in healthy people. (5, 6, 9)

SS-B (anti-La)- Even though SS-B is rarely present without SS-A and no longer used in the Classification Criteria, rheumatologists often like to see this test prior to referral because it may be  associated with organ involvement and certain cardiac arrhythmias.  SS-B is present in about 40 % of Sjogren’s patients.   Like SS-A, SS-B is seen in other CTDs, especially lupus, and sometimes in healthy people. (4, 5, 6, 9)

CCP (or ACPA) - Positive antibodies to CCPs in the presence of erosive arthritis is suggestive of RA.  However, these antibodies may be occasionally seen in Sjogren’s (3-10 %) (5, 11), SLE and other CTDs.   A rheumatologist’s expertise is needed for interpreting this test when a patient presents with ACPA along with clinical signs of Sjogren’s.

ANA (Anti-nuclear antibodies)-  Positive in 50-70 % of  Sjogren’s.  Seen in many other CTDs. (5, 6, 9)  Some healthy people carry ANA, although often at lower titers. (6)  Infections, liver disease and other conditions may also be associated with a positive ANA test. 

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

CRP and ESR- These inflammatory markers may be elevated or completely normal.  They are elevated in many conditions, generally indicating infection or inflammation.  High ESR  (“sed rate”) is common in Sjogren’s, reflecting high antibody levels in the blood.  ESR and CRP are not generally useful in assessing how active the disease is. 

CBC with diff and platelets-  Cytopenias of all types are common in Sjogren’s. They are usually mild and not associated with symptoms.  Severe thrombocytopenia or autoimmune hemolytic anemia are uncommon, but require management in by a hematologist when they occur. (10)

Serum Potassium-  Hypokalemia may indicate distal renal tubular acidosis, a kidney complication of Sjogren’s. (10)

UA, random urine protein and creatinine- Mild proteinuria is common in Sjogren’s, but usually occurs without symptoms.  About 5 %  of Sjogren’s patients have clinically significant kidney disease.  UTI and Interstitial cystitis, however, are  common due to chronic inflammation of bladder wall.  (10, 11

LFTs- May indicate liver and/or biliary tract disease.   Liver enzymes are elevated in about 7 %. (10, 13)

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

FAQ about autoantibody tests

How do autoantibodies help diagnose Sjogren’s and other CTDs?

In many patients with CTDs, autoantibodies can help clinicians distinguish between diseases that have overlapping manifestations.  The relationship between autoantibodies and various diseases can be complicated.  Many autoantibodies, including SS-A, are associated with more than one disease.

What role do antigen-antibody complexes have in the disease process?

Sjogren’s is considered to be an autoimmune disease.  Antigen-antibody complexes are thought to cause damage to salivary glands, lacrimal (tear) glands and organs.  However, the role that autoantibodies play in the disease process is not 100 % clear.  Many Sjogren’s patients do not carry autoantibodies.  Yet these “seronegative” patients also show tissue damage in MSGB specimens.  It is possible that more than one disease process causes clinical Sjogren’s.  There may be subtypes of Sjogren’s patients, with different underlying disease processes.  Researchers are trying to uncover the complex immunologic, genetic and cell biology changes that cause Sjogren’s.   

What exactly are “Sjogren’s Antibodies”?   

SS-A (anti-Ro) and SS-B (anti-La) have been traditionally called Sjogren’s antibodies. They are members of the family of antibodies called anti-nuclear antibodies (ANAs).   SS-A is now used without SS-B for Classification because patients who have SS-B alone are unlikely to have Sjogren’s.  (4, 6)   Currently, the term “seropositive” usually refers to positive SS-A.  Some researchers and rheumatologists may include ANA, SS-B, or RF along with SS-A in their definition of seropositivity.  This can be very confusing!

Why are some people SS-A positive and ANA negative?

Because SS-A is a type of antinuclear antibody, it is logical to expect ANA to be positive every time SS-A is positive.  However, some patients will test positive for SS-A and negative for ANA.   This is usually a problem with the test itself, especially if the laboratory uses the less sensitive solid phase ANA.

Not all ANA tests are the same

The cheap "qualitative", solid phase ANA is used by the vast majority of labs.  It only contains 8-10 autoantigens, while the IFA identifies over 100... therefore, more sensitive.   The ACR has actually come out with a position paper about it:

“The ACR supports the immunofluorescence antinuclear antibody (ANA) test using Human Epithelial type 2 (HEp-2) substrate, as the gold standard for ANA testing.”

 http://www.rheumatology.org/Portals/0/Files/Methodology%20of%20Testing%20Antinuclear%20Antibodies%20Position%20Statement.pdf

~ Personal Communication from, Donald E. Thomas, Jr., M.D., FACP, FACR, RhMSUS, CCD, Author of "The Lupus Encyclopedia"

What are ANA staining patterns?

 “The pattern of the ANA test can give information about the type of autoimmune disease present and the appropriate treatment program. A homogenous (diffuse) pattern appears as total nuclear fluorescence and is common in people with systemic lupus. A peripheral pattern indicates that fluorescence occurs at the edges of the nucleus in a shaggy appearance; this pattern is almost exclusive to systemic lupus. A speckled pattern is also found in lupus. Another pattern, known as a nucleolar pattern, is common in people with scleroderma.”

https://www.hopkinslupus.org/lupus-tests/lupus-blood-tests/

Sjogren’s more typically has a speckled pattern, although this is not specific to Sjogren’s.      

Do titers of ANA and SS-A correlate with disease severity or activity? Should these tests be used to follow the disease?

No and No!  There is no need to repeat these tests for diagnosis once a positive SS-A is obtained.  Sometimes SS-A and ANA may be repeated by a rheumatologist for reasons other than diagnosis.  Titers of SS-A and or ANA going up and down do not reflect disease severity. (6)

No single test can tell you "how sick you are"

At this time, there is no test that measures overall disease activity in Sjogren’s. ESSDAI and ESSPRI are research tools for measuring disease activity, although they are rarely used in the clinic setting.(10)

"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

Other tests that can support a Sjogren's diagnosis

There are many other tests that can help point to a Sjogren’s diagnosis.  Laboratory markers, such as cytopenias and hypergammaglobulinemia are common in Sjogren’s.  Rheumatologists often consider these as part of the clinical picture that suggests a Sjogren’s diagnosis. (3)

There are tests that help determine risk for organ system involvement or lymphoma. This will be discussed in more detail in other sections. 

New diagnostic tests

New biomarkers are being investigated, including PSP (parotid secretory protein),  CA-6 (carbonic anhydrase VI) various tear proteins (9, 15) and others.  At this time these tests do not appear to be more sensitive in diagnosing Sjogren’s. These tests and others are in the early stages of investigation.

Salivary Gland Ultrasound may eventually replace MSGB, which is invasive and has been shown to produce false positive and false negative results.  However, the focus score and presence of germinal centers in MSGB may correlate with disease characteristics, making the test useful for uncovering certain high risk populations.  (3, 14 ,16)

PLEASE NOTE:  These labs are discussed in the context of diagnosis only.  There are many additional tests used for ongoing monitoring and care.   

Updated 4-23-19