Abstract
BackgroundAnnexins are a group of conserved proteins which exert several regulatory functions on various cellular activities. Increased frequency and levels of antibodies against annexin V have already been observed in several autoimmune diseases including systemic sclerosis (SSc), but their role as a vascular biomarker is unknown. The aim of this study was to determine the serum levels and the dynamical behavior of anti-annexin V antibodies over a 24 months follow-up in patients with SSc.MethodsIn this bicentric cross-sectional study, 70 patients with SSc were consecutively selected from March 2016 to April 2017. Demographic and clinical features, including the presence of active DUs, were collected. Serum anti-annexin V IgG and IgM antibodies were measured at baseline and after 6, 12 and 24 months of follow-up. Videocapillaroscopy was performed in all patients.ResultsAmong the 70 SSc patients included anti-annexin V IgG was found in 11 patients (15.7%) (range of 15.88–39.48 U/mL) and anti-annexin V IgM in 10 patients (14.3%) (range of 14.16–22.69 U/mL) at baseline. During follow-up, the number of patients who were positive for anti-annexin V IgG and IgM remained stable over 24 months. Among the patients with positive anti-annexin V IgG at baseline the frequency of patients with necrosis or amputation of extremities, forced vital capacity less than 70% and pulmonary arterial hypertension (PAH) was significantly higher than in patients with negative anti-annexin V IgG antibodies. Patients with anti-annexin V IgG had also a higher Raynaud’s Condition Score and a higher Health Assessment Questionnaire Disability Index (HAQ-DI) than patients without these antibodies at baseline. Patients with positive anti-annexin V IgM at baseline presented a higher frequency of PAH, compared to those with negative anti-annexin V IgM at baseline.ConclusionsAnti-annexin V antibodies are stable and do not change their positivity during a 24 month follow-up in SSc patients. Anti-annexin V IgG was associated with more severe interstitial lung involvement and digital microangiopathy, and patients with anti-annexin V IgG or IgM had a higher occurrence of PAH indicating an association of these biomarker with more severe disease.
Highlights
Systemic sclerosis (SSc) is an autoimmune connective tissue disease, characterized by heterogeneous clinical presentation that affects the skin and several internal organs [1]
Autoantibodies directed toward annexin I, II, V and XI have been reported in different autoimmune diseases, including autoimmune rheumatic diseases, but their role in immune response is controversial [9]
We evaluated the association of antiannexin V antibodies with the severity of peripheral vasculopathy, digital ulcers occurrence and the microvascular changes observed in nailfold videocapillaroscopy during follow-up
Summary
Systemic sclerosis (SSc) is an autoimmune connective tissue disease, characterized by heterogeneous clinical presentation that affects the skin and several internal organs [1]. The pathogenesis of SSc includes interplay between vascular injury, abnormalities of the cellular and humoral immune systems and tissue fibrosis of the skin and internal organs such as lung, heart, and gastrointestinal tract [2, 3]. Annexin V is highly expressed by vascular endothelial cells and is involved in the regulation of apoptosis and protection against both excessive coagulation and inflammatory activities [12,13,14]. Increased frequency and levels of antibodies against annexin V have already been observed in several autoimmune diseases including systemic sclerosis (SSc), but their role as a vascular biomarker is unknown. The aim of this study was to determine the serum levels and the dynamical behavior of anti-annexin V antibodies over a 24 months follow-up in patients with SSc
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