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. 2016 Feb;68(2):254-60.
doi: 10.1002/acr.22632.

Association of Antibodies to Interferon-Inducible Protein-16 With Markers of More Severe Disease in Primary Sjögren's Syndrome

Alan N Baer  1 , Michelle Petri  1 , Jungsan Sohn  1 , Antony Rosen  1 , Livia Casciola-Rosen  1
Affiliations

Association of Antibodies to Interferon-Inducible Protein-16 With Markers of More Severe Disease in Primary Sjögren's Syndrome

Alan N Baer et al. Arthritis Care Res (Hoboken). 2016 Feb.

Abstract

Objective: Interferon-inducible protein-16 (IFI16) is an intracellular DNA receptor involved in innate immunity. We evaluated the frequency, phenotypic characteristics, and clinical associations of anti-IFI16 antibodies in patients with primary Sjögren's syndrome (SS), and quantitated expression levels of IFI16 in SS and control salivary gland lysates.

Methods: Anti-IFI16 antibodies were assayed by enzyme-linked immunosorbent assay using sera from patients with primary SS (n = 133) and from healthy controls (n = 47). Sera from systemic lupus erythematosus (SLE) patients (n = 132) were included as disease controls. Immunoprecipitation of in vitro transcription-translated IFI16 was used to determine which portion of IFI16 the antibodies recognized. Expression of IFI16 in salivary gland lysates was quantitated by immunoblotting.

Results: Anti-IFI16 antibodies were present in the sera of 38 of 133 SS patients (29%) compared to 1 of 47 healthy controls (2.1%) (SS versus controls; P < 0.0002) and in 31 of 132 SLE controls (24%). In SS, anti-IFI16 antibodies were associated with an abnormal Schirmer's test (P = 0.003), hyperglobulinemia (P = 0.02), antinuclear antibody ≥1:320 (P = 0.01), germinal center-like structures in labial salivary gland lymphoid infiltrates (P = 0.01), and higher focus scores (3.4 versus 2.4; P = 0.005). High-titer IFI16 antibodies were directed against an epitope outside the N-terminus in 9 of 13 SS patients (69%). IFI16 was expressed in 4 of 5 (80%) of SS and 1 of 6 (17%) of control labial salivary glands.

Conclusion: Anti-IFI16 antibodies are a prominent specificity in primary SS and are associated with markers of severe disease. IFI16 is expressed at higher levels in SS salivary glands compared to controls. These high levels in disease target tissue may contribute to the ongoing anti-IFI16 immune response.

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Conflict of interest statement

Conflicts of interest: None of the authors has received any financial support or other benefits from commercial sources for the work reported in this manuscript, nor do any of the authors have any other financial interests which could create a potential conflict of interest, or the appearance thereof.

Figures

Figure 1
Figure 1. Antibodies against IFI16 are detected in patients with SS, but not in healthy controls
Serum IgG antibodies against IFI16 were assayed by ELISA in patients with SS (n = 133) and healthy controls (n = 47), as described in the Methods and Results sections. Each symbol represents the IFI16 antibody level in a single patient serum. Antibodies were detected in 38/133 (29%) of SS patients, and 1/47 (2.1%) of controls. The dotted line marks the cutoff for assignment of a positive score.
Figure 2
Figure 2. Biochemical levels of IFI16 are elevated in salivary gland lysates from SS patients
Lysates were made from frozen salivary gland (SS and controls). Equal protein amounts were immunoblotted with an antibody against IFI16 (upper panel). The blotted bands migrated at 95 and 85 kDa. In each lysate, β-actin was immunoblotted as a loading control. The data were quantitated as described in the Methods Section, and IFI16 levels (normalized in each case relative to β-actin in the same lysate) are represented as box plots (lower panel). Levels of IFI16 in SS salivary glands were significantly higher than in control salivary glands (p = 0.004).
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