Systemic sclerosis (SSc) is a connective tissue disease characterized by extensive fibrosis of the skin and internal organs, associated with vasculopathy and autoimmune features. Antinuclear antibodies (ANA) are found in almost all SSc patients and constitute strong diagnosis and prognosis biomarkers. However, it remains unclear whether ANA are simple bystanders or if they can have a role in the pathophysiology of the disease. One might think that the nuclear nature of their targets prevents any accessibility to autoantibodies. Nevertheless, recent data suggest that ANA could be pathogenic or at least contribute to the perennation of the disease. We review here first the indirect clues of the contribution of ANA to SSc: they are associated to the disease subtypes, they may precede disease onset, their titer correlates with disease activity and severity, there is an association between molecular subsets, and some patients can respond to B-cell targeting therapy. Then, we describe in a second part the mechanisms of ANA production in SSc from individual genetic background to post-transcriptional modifications of neoantigens. Finally, we elaborate on the potential mechanisms of pathogenicity: ANA could be pathogenic through immune-complex-mediated mechanisms; other processes potentially involve molecular mimicry and ANA penetration into the target cell, with a focus on anti-topoisomerase-I antibodies, which are the most probable candidate to play a role in the pathophysiology of SSc. Finally, we outline some technical and conceptual ways to improve our understanding in this field.

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Background:Systemic sclerosis (SSc) is an autoimmune disorder that is characterized by a interplay of vascular abnormalities, immune system activation and an uncontrolled fibrotic response associated with interstitial lung disease affecting about 40% of patients. Identification of ILD relies on high-resolution CT that identify features suggestive of the histologic patterns of SSc(1). CT is used to determine pattern and extent of ILD and participates in the prediction of ILD progression(2).All group of pulmonary hypertension (PH) may occur with an overall prevalence reported in up to one fifth of patient. Whereas extensive SSc-ILD can be responsible for PH, PH can also be seen as a consequence of myocardial abnormalities or as primarily affecting small pulmonary arteries and classified as pulmonary arterial hypertension.Dual-energy CT introduction offers perspectives in the evaluation of SSc-related pulmonary manifestations. While these are not strictly perfusion images, they have been reported as adequate surrogate markers of lung perfusion (3). In the field of PH, detection of perfusion defects highly concordant with V/Q scintigraphic findings has been reported in the diagnostic approach of CTEPH but also in the differential diagnosis between PAH and peripheral forms of CTEPH (4).Objectives:To investigate lung perfusion abnormalities in patients with SSc.Methods:The study population included 101 patients who underwent dual-energy CT (DECT) angiography in the follow-up of SSc. CT examinations were obtained on a 3rd-generation dual-source CT system with reconstruction of morphologic and perfusion images. All patients underwent pulmonary function tests within two months of the follow-up CT scan. Fifteen patients had right heart catheterization-proven PH.Results:Our population included patients without SSc lung involvement (Group 1; n=37), patients with SSc-related ILD (Group 2; n=56) of variable extent (Group 2a: ≤10%: n=17; Group 2b: between 11-50%: n=31; Group 2c: >50%: n=8) and patients with PVOD/PCH (Group 3; n=8). Lung perfusion was abnormal in 8 patients in G 1 (21.6%), 14 patients in G 2 (25%) and 7 patients in G 3 (87.5%). Perfusion changes were mainly composed of bilateral perfusion defects, including patchy, PE-type perfusion defects and areas of hypoperfusion of variable size. In G 1 and G 2a (n=54): (a) patients with abnormal lung perfusion (n=14) had a significantly higher proportion of NYHA III/IV scores of dyspnea (p=0.031), a shorter mean walking distance at the 6MWT (p=0.042) and a trend towards lower mean DLCO% (p=0.055) when compared to patients with normal lung perfusion (n=40); (b) a negative albeit weak correlation was found between the iodine concentration in both lungs and the DLCO% (r=-0.27; p=0.059) whereas no correlation was found with PAPs (r=0.16; p=0.29) and walking distance during the 6MWT (r=-0.029; p=0.84).Conclusion:DECT lung perfusion provides complementary information to HRCT scans, depicting perfusion changes in SSc patients with normal or minimally infiltrated lung parenchyma.References:[1]Kim EA, Lee KS, Johkoh T, Kim TS, Suh GY, Kwon OJ, et al. Interstitial lung diseases associated with collagen vascular diseases: radiologic and histopathologic findings. Radiogr Rev Publ Radiol Soc N Am Inc. 2002 Oct;22 Spec No:S151-165.[2]Goh NSL, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1248–54.[3]Fuld MK, Halaweish AF, Haynes SE, Divekar AA, Guo J, Hoffman EA. Pulmonary perfused blood volume with dual-energy CT as surrogate for pulmonary perfusion assessed with dynamic multidetector CT. Radiology. 2013 Jun;267(3):747–56.[4]Giordano J, Khung S, Duhamel A, Hossein-Foucher C, Bellèvre D, Lamblin N, et al. Lung perfusion characteristics in pulmonary arterial hypertension and peripheral forms of chronic thromboembolic pulmonary hypertension: Dual-energy CT experience in 31 patients. Eur Radiol. 2017 Apr;27(4):1631–9.Disclosure of Interests:None declared

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