Association between centromere and topoisomerase specific immune responses and the degree of microangiopathy in Systemic Sclerosis.

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Autoreactive antibody responses, including the use of several isotypes of autoantibodies, have been shown to associate with clinical outcome in several rheumatic autoimmune diseases. The goal of this study was 1) to evaluate whether anti-centromere antibody(ACA) and anti-topoisomerase antibody(ATA) specific isotype expression and 2) organ involvement associate with the degree of microangiopathy in SSc.ACA and ATA IgG, IgM and IgA levels were measured in baseline serum samples of ACA IgG+ and ATA IgG+ SSc patients. The degree of microangiopathy was determined based on nailfold videocapillaroscopy images at the same time point. Logistic regression analyses with autoantibodies, clinical characteristics, isotype expression and ACA resp. ATA IgG, IgM and IgA levels as independent and NVC pattern as dependent variable were performed.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 3.1 (1.4-6.6)), interstitial lung disease(OR 3.2 (1.1-9.7)) and pulmonary arterial hypertension(OR 5.25 (1.69-16.36)). ATA positivity was associated with more severe microangiopathy(OR 2.09 (1.05-4.13)). Patients that solely expressed ACA IgG showed a trend towards less severe microangiopathy compared to patients expressing also ACA IgM and/or IgA, levels of ACA IgG and ATA IgM associated with microangiopathy severity.We observed an association between ACA and ATA responses and the degree of microangiopathy in SSc. These findings might indicate that the breath of the autoimmune response as reflected by autoantibody production and microvascular damage interact in the pathophysiology of SSc.


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