POS0869 PREDICTIVE VALUE OF ANTI-INTERFERON-INDUCIBLE PROTEIN 16 ANTIBODIES FOR DIGITAL ULCERS OF SYSTEMIC SCLEROSIS
Authors: C. Chen, S. Yang, Z. Jiang, W. Wan, H. Zou, M. Liang
Journal: Annals of the Rheumatic Diseases (2021)

Background: Interferon-inducible protein 16 (IFI-16) is constitutively expressed in vascular endothelial cells and can inhibit the proliferation of human endothelial cells and the formation of capillary-like structures in vitro. Anti-IFI-16 antibodies were reported in 21%-29% of patients with systemic sclerosis (SSc) and were associated with digital vascular events in a few retrospective studies. Objectives: To evaluate the presence and the clinical implication of anti-IFI-16 antibodies in Chinese SSc cohort, focusing on the associations with vasculopathy indexes, and to investigate the predictive value of anti-IFI-16 antibodies for the development of digital ulcers (DUs) in SSc prospectively. Methods: Patients with SSc presenting to our center between July 2018 and September 2018 were prospectively enrolled. Serum from 42 SSc patients and 42 age- and sex-matched healthy controls were analyzed for anti-IFI-16 antibodies by enzyme-linked immunosorbent assay (ELISA), and was considered positive if the optical density (OD) value was above the mean OD of controls plus two standard deviations. Tissue immunofluorescence was used to evaluate the expression of IFI16 in skin biopsy samples obtained from SSc patients and normal controls. At baseline, nailfold video-capillaroscopy was performed to assess nailfold capillary density of SSc patients. Power Doppler ultrasound was used to grade finger pulp blood flow (0-no observed flow; 1-decreased flow; 2-normal flow), and to measure ulnar and radial artery blood flow and resistive index (RI). All patients were followed up for 6 months to see whether they experienced new onset or recurrent DUs. The association of anti-IFI-16 antibodies with DUs was analyzed using logistic regression. Results: Of the 42 SSc patients, 8 (19.0%) were positive for anti-IFI-16 antibodies. Immunofluorescence of skin biopsy samples from SSc patients exhibited enhanced staining of IFI-16 in the dermis, and colocalization with endothelial marker CD31. SSc patients who were positive for anti-IFI-16 antibodies showed higher ulnar artery RI at baseline (0.95±0.09 vs. 0.86±0.09, p=0.015), while no significant differences were found for other vascular parameters, nor for clinical or demographic profiles. Within 6-month follow-up, 14 (33.3%) patients experienced new-onset or recurrent DUs. Univariate logistic regression revealed the presence of DUs at enrollment (p=0.009), anti-IFI-16 antibody (p=0.012), finger pulp blood flow (p=0.027), and ulnar artery RI (p=0.008) could be the predictors for the development of DUs. Multivariate analysis further identified DUs at enrollment (odds ratio [OR]: 10.85; 95% confidence interval [CI]: 1.61-73.18; p=0.014) and anti-IFI-16 antibody (OR: 15.00; 95% CI: 1.13-199.18; p=0.040) as independent risk factors. Among patients without DUs at enrollment, new-onset ulcers occurred in 80% (4/5) and 4.5% (1/22) of those with and without anti-IFI-16 antibody, respectively (p=0.001). Conclusion: Anti-IFI-16 antibody is associated with vasculopathy in SSc and could be used as a novel biomarker for indicating the development of DUs. References: [1]McMahan ZH, Shah AA, Vaidya D, et al. Anti-interferon-inducible protein 16 antibodies associate with digital gangrene in patients with Scleroderma. Arthritis Rheumatol. 2016; 68(5): 1262-71. [2]McMahan ZH, Cottrell TR, Wigley FM, et al. Autoantigens targeted in scleroderma patients with vascular disease are enriched in endothelial lineage cells. Arthritis Rheumatol. 2016; 68(10): 2540–49. Figure 1. Multivariate logistic analysis for new or recurrent digital ulcers. Acknowledgements: The authors would like to thank Doctor Yi Cheng for performing Power Doppler ultrasound assessment. Disclosure of Interests: None declared