Background/Purpose: The validity of low titers of SSA and/or SSB (SSA/B) antibodies (Ab) in the diagnosis of Sjögren’s syndrome (SS) has not been defined. We explored the validity of using varying SSA/B-ab titers to predict a “positive lip biopsy”, a known objective test used in the ACR classification of SS (Arth Care Res 2012;64:375).
Methods: SICCA is an NIH-funded registry in which patients with suspected or established SS undergo a uniform evaluation, including minor salivary gland (lip) biopsy. SSA/B-Ab testing was performed by Quest Laboratories, using a multiplex flow immunoassay. Positive results were expressed in “antibody index” (AI) units and as continuous measure variables up to a level of 8 AI, beyond which the units were not quantified. We defined “low titer” SSA/B-Ab as those between 1 and 8 AI. A “positive lip biopsy” was defined as focal or focal/sclerosing lymphocytic sialadenitis with a focus score ≥ 1. The validity of SSA/B-Ab testing was defined by the degree to which patients were correctly classified as having or not having a positive lip biopsy, used in lieu of a gold standard. This was quantified by sensitivity and specificity across the range of AI units for 1) SSA-Ab alone, 2) SSB-Ab alone, and 3) combinations of SSA/B-Ab.
Results: Of the 1,861 SICCA patients, the mean age was 53, 91% were female and 629 (34%) had a positive lip biopsy. For SSA-Ab, 431 (23%) >8 AI and 139 (7%) had low titers. For SSB-Ab, 184 (9%) >8 AI and 168 (9%) had low titers. SSA- and SSB-Ab > 8 AI had unacceptably low sensitivity (see Table). With increasing SSA-Ab cutoff levels, the likelihood of misclassifying a patient with a negative lip biopsy decreased (specificity 84 → 91%) while the likelihood of not identifying a patient with a positive lip biopsy increased (sensitivity 60 → 51%). Use of the SSB-Ab test alone was associated with high specificity but low sensitivity. In the combined analysis, the sensitivity and specificity respectively, were, 1) SSA-Ab≥1 & SSB-Ab<1: 0.35 & 0.89; 2) SSA-Ab≥1 & SSB-Ab≥1: 0.51 & 0.94; 3) SSA-Ab<1 & SSB-Ab≥1: 0.05 & 0.98 and; 4) SSA-Ab>1 or SSB-Ab>1: 0.62 & 0.82. Results were similar when the study was restricted to those patients with an objective parameter indicative of dry eye syndrome.
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Table: Sensitivity, Specificity and 95% Confidence Intervals by SSA/B Threshold |
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SSA test alone |
SSB test alone |
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SSA/SSB Threshold |
Sensitivity |
Specificity |
Sensitivity |
Specificity |
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> 1 |
0.60 (0.56, 0.64) |
0.84 (0.82, 0.86) |
0.41 (0.38, 0.45) |
0.93 (0.91, 0.94) |
|
> 2 |
0.59 (0.55, 0.63) |
0.86 (0.84, 0.88) |
0.35 (0.31, 0.39) |
0.94 (0.93, 0.96) |
|
> 3 |
0.58 (0.54, 0.62) |
0.87 (0.85, 0.88) |
0.32 (0.28, 0.36) |
0.95 (0.94, 0.96) |
|
> 4 |
0.57 (0.53, 0.61) |
0.88 (0.86, 0.89) |
0.29 (0.26, 0.33) |
0.96 (0.94, 0.97) |
|
> 5 |
0.56 (0.52, 0.60) |
0.89 (0.87, 0.90) |
0.28 (0.24, 0.31) |
0.96 (0.95, 0.97) |
|
> 6 |
0.52 (0.49, 0.56) |
0.90 (0.88, 0.91) |
0.26 (0.23, 0.30) |
0.97 (0.95, 0.98) |
|
>7 |
0.52 (0.48, 0.56) |
0.90 (0.89, 0.92) |
0.25 (0.22, 0.29) |
0.97 (0.96, 0.98) |
|
>8 |
0.51 (0.47, 0.55) |
0.91 (0.89, 0.93) |
0.24 (0.21, 0.27) |
0.97 (0.96, 0.98) |
Conclusion: SSA- and SSB-Ab > 8AI had low sensitivity and the inclusion of low titers resulted in a minimal improvement in the test’s moderate sensitivity and minimal decrease in specificity. This confirms the need to perform additional objective tests, such as a lip biopsy, in the diagnosis of SS.
Disclosure:
M. McAdams DeMarco,
None;
M. Y. Lam,
None;
S. Shiboski,
None;
L. A. Criswell,
None;
C. Shiboski,
None;
A. N. Baer,
None.
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