Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Interferon inducible protein-16 (IFI16) is an intracellular DNA receptor involved in innate immunity. We evaluated the frequency and clinical significance of anti-IFI16 antibodies in cohorts of primary Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE), and dermatomyositis (DM). Expression levels of IFI16 in relevant target tissues were quantified.
Methods: Anti-IFI16 antibodies were assayed by ELISA using sera from patients with primary SS (n=133; Sjögren’s International Collaborative Clinical Alliance Biorepository), SLE (n=132: Hopkins Lupus Cohort), DM (n=114; Stanford Dermatology Clinic) and healthy controls (n=47). Immunoprecipitation was used to determine whether antibodies recognized the N-or C-terminus. Expression of IFI16 in lysates made from salivary gland and skin was quantified by immunoblotting.
Results:
Anti-IFI16 antibodies were present in 38/133 (29%) SS, 31/132 (23.5%) SLE, and 3/114 (2.6%) DM patients, and 1/47 (2.1%) controls (SS vs controls, p<0.0002; SLE vs controls, p=0.0006; DM vs controls, p=1.0). The levels of anti-IFI16 antibodies were higher in SS [median (25th-75th percentile): 0.334 (0.244-0.591)] as compared to SLE [0.242 (0.164-0.477); p=0.0002]. In SS, anti-IFI16 antibodies were associated with an abnormal Schirmer’s test (p=0.0032), IgG> 1445 mg/dl (p=0.0189), ANA ≥1:320 (p=0.0152), germinal centers (p=0.0130), and higher rheumatoid factor levels [median (25th-75th percentile): 56.5 IU/ml (10.75-97) vs 25 (8-54), p=0.0132] and focus scores [3.4 (2.63-6.38) vs 2.4 (1.6-3.7), p=0.0053 ]. With the exception of germinal centers, these associations remained significant in the subgroup of 98 SS patients with positive SSA/B serology. In SLE, this specificity was associated with anti-DNA antibodies (p=0.0017). Among patients with high antibody levels, anti-IFI16 antibodies were directed against the C-terminus in 9/13 (69%) SS and 4/15 (26.7%) SLE patients (p=0.056). DNA antibodies were present in 10/11 (91%) of the SLE patients with antibodies to the N-terminus and in 1/4 (25%) of the patients with antibodies to the C-terminus (p=0.033). IFI16 was expressed in 4/5 (80%) of SS and 1/6 (16.7%) of control labial glands, and 4/8 (50%) of SLE skin and 0/3 (0%) of control skin biopsies.
Conclusion: Anti-IFI16 antibodies are found in primary SS and SLE with similar frequencies (24-29%), but not in DM, despite a role for interferon in the pathogenesis of all 3 diseases. These antibodies correlate with a more severe phenotype in SS and with the presence of DNA antibodies in SLE. Anti-IFI16 antibodies target different portions of the molecule in SS and SLE. Expression of IFI16 in relevant target tissues correlates with the presence of antibody to this molecule.
Research supported by NIH/NIDCR contract HHSN26S201300057C
Disclosure:
A. N. Baer,
None;
M. Petri,
None;
D. Fiorentino,
None;
T. Wang,
None;
J. Sohn,
None;
A. Rosen,
None;
L. Casciola-Rosen,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibodies-to-human-interferon-inducible-protein-16-are-present-in-primary-sjogrens-syndrome-and-systemic-lupus-but-are-rare-in-dermatomyositis/