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Sjogren Syndrome: Laboratory Support of Diagnosis

Sjogren Syndrome: Laboratory Support of Diagnosis

Clinical Focus

Sjögren Syndrome

Laboratory Support of Diagnosis

  

Contents:

Clinical Background

Individuals Suitable for Testing

Test Availability - Table 1

Test Selection

Test Interpretation - Table 2

References
 

Clinical Background [return to contents]

Sjögren syndrome is an autoimmune disease characterized by lymphocyte infiltration of exocrine glands, which manifests as dry eyes and mouth.1 The syndrome is estimated to be between 9 and 20 times more common in women than in men and typically presents in the 4th or 5th decade of life.1 The disease can present by itself (primary) or in association with another underlying autoimmune condition (secondary), commonly rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).2 Sjögren syndrome may occur as part of a triad that includes primary biliary cirrhosis (PBC) and autoimmune thyroid disease.1,2 Patients with Sjögren's syndrome also have an overall increased risk for malignancies, specifically non-Hodgkin lymphoma and thyroid cancer.3

Although dry eyes are the hallmark of the condition, initial symptoms can be nonspecific and may include mild dry mouth, arthralgias, and fatigue.1 These nonspecific symptoms, coupled with a general lack of awareness of the disease, can delay diagnosis up to 7 years.4 Prompt diagnosis, however, is important as early treatment can prevent progression to complete loss of lacrimal and salivary gland function and extraglandular involvement including synovitis, interstitial lung disease, neuropathy, vasculitis, and renal disease.1

Individuals Suitable for Testing [return to contents]

  • Individuals suspected of having Sjögren syndrome
  • Individuals suspected of having an autoimmune condition associated with Sjögren syndrome

Test Availability [return to contents]

Test availability is shown in Table 1.

Table 1. Tests Used to Diagnose Sjögren Syndrome and Associated Disorders

Test Code

Test Name

Clinical Use

249a

ANA Screen, IFA with Reflex to Titer and Pattern

Diagnose Sjögren syndrome and other rheumatic conditions, including RA and SLE

90077a

ANA Screen, IFA, with Reflex to Titer and Pattern (Sjögren's Panel 1)

Includes ANA screen (IFA) with reflex to titer and pattern; also includes rheumatoid factor and SS-A and SS-B antibodies.

Diagnose Sjögren syndrome with or without RA

19880(X)a

ANA Screen, IFA, with Reflex to Titer and Pattern (Sjögren's Panel 2)

Includes ANA screen (IFA) with reflex to titer and pattern; mitochondrial antibody screen with reflex to titer; rheumatoid factor; and SS-A, SS-B, and thyroid peroxidase antibodies.

Diagnose Sjögren syndrome and assess for concurrent PBC or autoimmune thyroid disease

93748

Early Sjögren’s Syndrome Profile

Includes carbonic anhydrase 6 IgG, IgM, IgA; parotid secretory protein IgG, IgM, IgA; and salivary gland protein (SP1) IgG, IgM, IgA.

Diagnose Sjögren syndrome at an early stage

259a

Mitochondrial Antibody with Reflex to Titer

Diagnose PBC

4418

Rheumatoid Factor

Diagnose Sjögren syndrome, RA, and PBC

7832

Sjögren’s Antibodies (SS-A, SS-B)

Diagnose Sjögren syndrome

38568

Sjögren’s Antibody (SS-A)

Diagnose Sjögren syndrome

38569

Sjögren’s Antibody (SS-B)

Diagnose Sjögren syndrome

5081

Thyroid Peroxidase Antibodies (TPO)

Diagnose autoimmune thyroid disease

ANA, antinuclear antibody; IFA, immunofluorescence assay; PBC, primary biliary cirrhosis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SS-A, Sjögren syndrome-related antigen A; and SS-B, Sjögren syndrome-related antigen B.
a Reflex tests are performed at an additional charge and are associated with an additional CPT code(s).

Test Selection [return to contents]

While a number of different diagnostic criteria for Sjögren syndrome have been proposed, Sjögren's International Collaborative Clinical Alliances Cohort/American College of Rheumatology criteria require at least 2 of the following to diagnose Sjögren syndrome: 1) positive Sjögren syndrome-related antigen A (SS-A, ie, Ro) and/or Sjögren syndrome-related antigen B (SS-B, ie, La) antibodies or positive rheumatoid factor (RF) and antinuclear antibodies (ANA); 2) positive minor salivary gland biopsy with a focus score ≥1/4 mm2; and 3) keratoconjunctivitis sicca with an ocular staining score ≥3.1

Salivary gland biopsy, however, is not commonly performed in clinical practice; thus, autoantibody detection plays a large role in the diagnosis. The key antibodies (SS-A, SS-B, RF, and ANA) can be complemented with mitochondrial and thyroid peroxidase antibodies to rule-in or rule-out the presence of concurrent PBC and autoimmune thyroid disease.

Autoantibodies to carbonic anhydrase 6 (CA6), salivary gland protein 1 (SP-1), and parotid secretory protein (PSP) have recently been identified in patients meeting Sjögren syndrome criteria. These 3 antibodies may assist in establishing a diagnosis of Sjögren syndrome earlier in the course of the disease, potentially leading to earlier treatment and reduced risk of end organ damage.1,5

Test Interpretation [return to contents]

Antibodies to SS-A and SS-B are consistent with a diagnosis of Sjögren syndrome1 but may also be seen in autoimmune thyroiditis,6 SLE,7 PBC,8 and RA.1 Absence of SS-A and SS-B antibodies does not rule out Sjögren syndrome, especially early in the disease course.1,6-8 These antibodies are often not identified until significant end organ damage has occurred.1 SS-A antibodies are found in up to 74% of patients with Sjögren syndrome, while SS-B antibodies are found in up to 52%.1

The presence of ANA and RF antibodies is consistent with Sjögren syndrome. Up to 85% of those with the syndrome have ANA antibodies, while up to 74% have RF antibodies.1 These antibodies are also seen in other autoimmune diseases (eg, RA, SLE), so their presence is not sufficient for a diagnosis.

Antibodies to CA6 and/or SP-1 are also consistent with Sjögren syndrome.5 Of patients with idiopathic dry mouth and dry eyes for <2 years, 76% had antibodies to CA6 and/or SP-1, while only 31% had antibodies to SS-A and/or SS-B.5 SP-1 has also been identified in 19% of Sjögren patients that are SS-A/SS-B negative.9 These data, in conjunction with mouse studies, seem to indicate that CA6 and SP-1 appear earlier in the disease and thus can be used to diagnose Sjögren syndrome at an earlier stage.5,10

PSP antibodies have been identified in 18% of patients with Sjögren syndrome and are rarely seen in normal controls.5 They have also been identified in 10% of patients with RA.5 If these early data are confirmed, PSP antibody presence may help identify patients with Sjögren syndrome who lack antibodies more commonly associated with the disease.5

Mitochondrial and thyroid peroxidase antibodies can help identify Sjögren syndrome patients with concurrent PBC and/or autoimmune thyroid disease.

The frequencies of the various autoantibodies in Sjögren syndrome and other autoimmune diseases are shown in Table 2. As some diagnostic criteria for Sjögren syndrome rely heavily on clinical signs and symptoms, laboratory results should be interpreted in light of a patient's clinical findings.1

Table 2. Antibody Frequency in Sjögren Syndrome and Associated Disorders1,5,6,8,11-14

Condition

Antibody Frequency, %

SS-A

SS-B

ANA

RF

CA6

SP-1

PSP

Mitochondrial

TPO

Sjögren
syndrome

33-74

23-52

59-85

36-74

54

54

18

5

9 (1°)

17 (2°)

SLE

30

10

98

20

 

 

 

 

 

RA

15

20

24

50

10

0

10

 

7

PBC

50

 

50

70

 

 

 

95

 

Autoimmune
thyroid

10a

 

35

 

 

 

 

 

83

1°, primary Sjögren syndrome; 2°, secondary Sjögren syndrome; ANA, antinuclear antibodies; CA6, carbonic anhydrase 6; PBC, primary biliary cirrhosis; PSP, parotid secretory protein; RA, rheumatoid arthritis; RF, rheumatoid factor; SLE, systemic lupus erythematosus; SP-1, salivary gland protein 1; TPO, thyroid peroxidase.
a Of ANA positive patients with autoimmune thyroid disease.

References [return to contents]

  1. Patel R, Shahane A. The epidemiology of Sjögren's syndrome. Clin Epidemiol. 2014;6:247-255.

  2. Tincani A, Andreoli L, Cavazzana I, et al. Novel aspects of Sjögren's syndrome in 2012. BMC Med. 2013;11:93. doi: 10.1186/1741-7015-11-93.

  3. Liang Y, Yang Z, Qin B,et al. Primary Sjogren's syndrome and malignancy risk: a systematic review and meta-analysis. Ann Rheum Dis. 2014;73:1151-1156.

  4. Improving diagnosis and outcomes of Sjögren's disease through targeting dry eye patients: a continuing medical education enduring material. Ocul Surf. 2015;13:S1-S33.

  5. Shen L, Suresh L, Lindemann M, et al. Novel autoantibodies in Sjögren's syndrome. Clin Immunol. 2012;145:251-255.

  6. Tektonidou MG, Anapliotou M, Vlachoyiannopoulos P, et al. Presence of systemic autoimmune disorders in patients with autoimmune thyroid diseases. Ann Rheum Dis. 2004;63:1159-1161.

  7. Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren syndrome. Arch Intern Med. 2004;164:1275-1284.

  8. Selmi C, Meroni PL, Gershwin ME. Primary biliary cirrhosis and Sjögren's syndrome: autoimmune epithelitis. J Autoimmun. 2012;39:34-42.

  9. Shen L, Kapsogeorgou EK, Yu M, et al. Evaluation of salivary gland protein 1 antibodies in patients with primary and secondary Sjögren's syndrome. Clin Immunol. 2014;155:42-46.

  10. Suresh L, Malyavantham K, Shen L, et al. Investigation of novel autoantibodies in Sjögren's syndrome utilizing sera from the Sjögren's International Collaborative Clinical Alliance Cohort. BMC Ophthalmol. 2015;15:38. doi: 10.1186/s12886-015-0023-1.

  11. Tunc R, Gonen MS, Acbay O, et al. Autoimmune thyroiditis and anti-thyroid antibodies in primary Sjögren's syndrome: a case-control study. Ann Rheum Dis. 2004;63:575-577.

  12. Witte T, Hartung K, Sachse C, et al. Rheumatoid factors in systemic lupus erythematosus: association with clinical and laboratory parameters. SLE study group. Rheumatol Int. 2000;19:107-111.

  13. Eriksson C, Engstrand S, Sundqvist KG, et al. Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF alpha. Ann Rheum Dis. 2005;64:403-407.

  14. Cozzani E, Drosera M, Gasparini G, et al. Serology of lupus erythematosus: correlation between immunopathological features and clinical aspects. Autoimmune Dis. 2014;2014:321359. doi: 10.1155/2014/321359.
     

Content reviewed 01/2016

 

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* The tests listed by specialist are a select group of tests offered. For a complete list of Quest Diagnostics tests, please refer to our Directory of Services.