RT Journal Article SR Electronic T1 Association Between Centromere- and Topoisomerase-specific Immune Responses and the Degree of Microangiopathy in Systemic Sclerosis JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP jrheum.191331 DO 10.3899/jrheum.191331 A1 Nina M. van Leeuwen A1 Corrie M. Wortel A1 Cynthia M. Fehres A1 Jaap A. Bakker A1 Hans U. Scherer A1 René E.M Toes A1 Tom W.J Huizinga A1 Jeska K. de Vries-Bouwstra YR 2020 UL http://www.jrheum.org/content/early/2020/12/10/jrheum.191331.abstract AB Objective Autoreactive antibody responses, including the use of several isotypes of autoantibodies, have been shown to be associated with clinical outcome in several rheumatic autoimmune diseases. The goals of this study were to evaluate whether (1) anticentromere antibody (ACA)– and antitopoisomerase antibody (ATA)–specific isotype expression, and (2) organ involvement are associated with the degree of microangiopathy in systemic sclerosis (SSc). Methods ACA and ATA IgG, IgM, and IgA levels were measured in baseline serum samples of ACA IgG–positive (+) and ATA IgG+ patients with SSc. The degree of microangiopathy was determined based on nailfold videocapillaroscopy (NVC) images collected at the same point in time. Logistic regression analyses with autoantibodies, clinical characteristics, isotype expression, and ACA and ATA IgG, IgM, and IgA levels as independent variables, and NVC pattern as the dependent variable were performed. Results In 164 patients, isotype levels and degree of microangiopathy were evaluated. Logistic regression confirmed the association of the degree of microangiopathy with the presence of digital ulcers (OR 3.07, 95% CI 1.43–6.60), interstitial lung disease (OR 3.41, 95% CI 1.11–10.61), and pulmonary arterial hypertension (OR 5.58, 95% CI 2.05–17.81). ATA positivity was associated with more severe microangiopathy (OR 2.09, 95% CI 1.05–4.13). Patients who expressed solely ACA IgG showed a trend towards less severe microangiopathy compared to patients also expressing ACA IgM and/or IgA. Levels of ACA IgG and ATA IgM were found to be associated with microangiopathy severity. Conclusion We observed an association between ACA and ATA responses and the degree of microangiopathy in SSc. These findings might indicate that the breadth of the autoimmune response, as reflected by autoantibody production and microvascular damage, interacts in the pathophysiology of SSc.