scholarly journals POS0869 PREDICTIVE VALUE OF ANTI-INTERFERON-INDUCIBLE PROTEIN 16 ANTIBODIES FOR DIGITAL ULCERS OF SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 690.1-690
Author(s):  
C. Chen ◽  
S. Yang ◽  
Z. Jiang ◽  
W. Wan ◽  
H. Zou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Logistic Regression ◽  
Power Doppler ◽  
Ulnar Artery ◽  
Digital Ulcers ◽  
Power Doppler Ultrasound ◽  
Inducible Protein ◽  
Interferon Inducible Protein ◽  
New Onset

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

scholarly journals AB0450 PERIPHERAL MACROVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS AS COMPARED WITH HEALTHY CONTROLS: A SMALL COHORT STUDY BY COLOR AND SPECTRAL DOPPLER ULTRASONOGRAPHY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1252.2-1252
Author(s):  
R. D’alessandro ◽  
E. Garcia Gonzales ◽  
P. Falsetti ◽  
C. Baldi ◽  
F. Bellisai ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Features ◽  
Doppler Ultrasonography ◽  
Power Doppler ◽  
Ulnar Artery ◽  
Artery Occlusion ◽  
Power Doppler Ultrasonography ◽  
Digital Ulcers ◽  
Healthy Controls ◽  
History Of

Background:Together with autoimmune-inflammation and fibrosis, microvasculopathy is a hallmark of SSc. However, also macrovascular changes may occur including peripheral proliferative vasculopathy. Whether this changes may represent a specific SSc marker with a predictive value remains a matter of debate.[1,2,3]Objectives:To study peripheral macrovascular involvement by color doppler ultrasound (CDUS) with spectral wave analysis (SWA) in a cohort of 40 SSc patients as compared to healthy controls. To further analyze any differences among the SSc population.Methods:Forty SSc patients and 36 healthy controls were examined by CDUS with SWA of both hands. Macrovascular involvement was assessed by measuring the resistivity index (RI) of distal ulnar and radial arteries. Examinations were performed with an Esaote MyLab Twice machine equipped with a linear 10-22 MHz probe. Ultrasound examination was carried out by two independent rheumatologists blinded to clinical conditions of the patients. Statistical analysis was performed by using MaxStat software.Results:The RI index resulted increased in the SSc cohort as compared with healthy controls (left ulnar RI 0.977 vs 0.715; right ulnar RI 0.996 vs 0.699; left radial RI 0.988 vs 0.706; right radial RI 0.999 vs 0.688; p<0.001). SSc patients with an increased RI in one artery were more probable to have an increased RI in the other vessels too (r 2 = 0.35; p<0.01). In addition, 8 out of 40 SSc patients presented left ulnar artery occlusion (UAO) and 7 out of 40 SSc patients presented right UAO, of which 6 presented bilateral UAO. Awaiting to enlarge the cohort for further analysis, descriptive data regarding increased RI at CDUS/SWA and clinical features, including years from onset of the disease, subtype of SSc, mRSS, history of digital ulcers, interstitial lung disease and PAH are described in Table 1.Conclusion:Peripheral macrovascular involvement was observed in SSc patients as compared with healthy controls. Further studies will determine whether this feature may have specificity for diagnosis/prognosis in SSc.References:[1]Lescoat A, Yelnik CM, Coiffier G et al. Ulnar Artery Occlusion and Severity Markers of Vasculopathy in Systemic Sclerosis: A Multicenter Cross-Sectional Study. Arthritis Rheumatol. 2019;71:983-990.[2]Lescoat A, Coiffier G, Rouil A et al. Vascular Evaluation of the Hand by Power Doppler Ultrasonography and New Predictive Markers of Ischemic Digital Ulcers in Systemic Sclerosis: Results of a Prospective Pilot Study. Arthritis Care Res (Hoboken). 2017;69:543-551.[3]Schioppo T, Orenti A, Boracchi P, De Lucia O, Murgo A, Ingegnoli F. Evidence of macro- and micro-angiopathy in scleroderma: An integrated approach combining 22-MHz power Doppler ultrasonography and video-capillaroscopy. Microvasc Res. 2019;122:125-130.Table 1.Main clinical features of the SSc cohort (n=40) studied by CDUS for macrovascular involvement.SSc cohort (n = 40)Years from onsetrange (35 y – 0 y)mean = 10.5 yAutoantibodiesACA 13/40Anti-TopoI 14/40Other 13/40mRSSrange (0 -30)mean = 3ILD17/40PAH7/40Capillaroscopy patternEarly 10/40Active 11/40Late 6/40History of digital ulcers16/40Left ulnar IR0.977Left radial IR0.988Right ulnar IR0.996Right radial IR0.999Disclosure of Interests:None declared.

scholarly journals Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells.

1993 ◽  
Vol 177 (6) ◽  
pp. 1809-1814 ◽  
Author(s):  
D D Taub ◽  
A R Lloyd ◽  
K Conlon ◽  
J M Wang ◽  
J R Ortaldo ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Biological Activity ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Inducible Protein ◽  
Interferon Inducible Protein

The human cytokine interferon-inducible protein 10 (IP-10) is a small glycoprotein secreted by activated T cells, monocytes, endothelial cells, and keratinocytes, and is structurally related to a family of chemotactic cytokines called chemokines. Although this protein is present in sites of delayed-type hypersensitivity reactions and lepromatous leprosy lesions, the biological activity of IP-10 remains unknown. We report here that recombinant human IP-10 stimulated significant in vitro chemotaxis of human peripheral blood monocytes but not neutrophils. Recombinant human IP-10 also stimulated chemotaxis of stimulated, but not unstimulated, human peripheral blood T lymphocytes. Phenotypic analysis of the stimulated T cell population responsive to IP-10 demonstrated that stimulated CD4+ and CD29+ T cells migrated in response to IP-10. This resembles the biological activity of the previously described T cell chemoattractant RANTES. Using an endothelial cell adhesion assay, we demonstrated that stimulated T cells pretreated with optimal doses of IP-10 exhibited a greatly enhanced ability to bind to an interleukin 1-treated endothelial cell monolayer. These results demonstrate that the IP-10 gene encodes for an inflammatory mediator that specifically stimulates the directional migration of T cells and monocytes as well as potentiates T cell adhesion to endothelium.

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