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

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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.

Original languageEnglish (US)
Pages (from-to)254-260
Number of pages7
JournalArthritis Care and Research
Volume68
Issue number2
DOIs
StatePublished - Feb 1 2016

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Interferons
Antibodies
Proteins
Salivary Glands
Lip
Systemic Lupus Erythematosus
Serum
Germinal Center
Antinuclear Antibodies
Immunoprecipitation
Immunoblotting
Innate Immunity
Epitopes
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Rheumatology

Cite this

@article{20de130b349146448966403360104295,
title = "Association of Antibodies to Interferon-Inducible Protein-16 with Markers of More Severe Disease in Primary Sj{\"o}gren's Syndrome",
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 Sj{\"o}gren'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.",
author = "Alan Baer and Michelle Petri and Jungsan Sohn and Antony Rosen and {Casciola Rosen}, {Livia A}",
year = "2016",
month = "2",
day = "1",
doi = "10.1002/acr.22632",
language = "English (US)",
volume = "68",
pages = "254--260",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "2",

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TY - JOUR

T1 - Association of Antibodies to Interferon-Inducible Protein-16 with Markers of More Severe Disease in Primary Sjögren's Syndrome

AU - Baer, Alan

AU - Petri, Michelle

AU - Sohn, Jungsan

AU - Rosen, Antony

AU - Casciola Rosen, Livia A

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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.

AB - 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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