Anti-annexin V autoantibodies and vascular abnormalities in systemic sclerosis: a longitudinal study

Abstract

Background: Annexins 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. Methods: In 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 antiannexin 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. Results: Among 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 followup, 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. Conclusions: Anti-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.

Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins

“…AnV aPL have been linked to a (pro)thrombotic state in several diseases including sickle cell disease [ 62 ] and APS [ 63 ]. Additionally, AnV IgG or IgM were associated with higher occurrence of pulmonary arterial hypertension and were detectable throughout a 2-year follow-up in patients with systemic sclerosis [ 64 ]. β2 and PT aPL were reported to cause LA (1) via direct interaction of β2 aPL with FV and activation by FXa and (2) via PT aPL competition with FXa for PL binding sites [ 65 ], actions which may account for the higher prevalence of LA described in patients with COVID-19 [ 13 ].…”

Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins

“…AnV aPL have been linked to a (pro)thrombotic state in several diseases including sickle cell disease (Sater et al ., 2011) and APS (Zhang et al ., 2017). Additionally, AnV IgG or IgM were associated with higher occurrence of pulmonary arterial hypertension and were detectable throughout a 2-year follow-up in patients with systemic sclerosis (Horimoto et al ., 2020). β2 and PT aPL were reported to cause LA (1) via direct interaction of β2 aPL with FV and activation by FXa and (2) via PT aPL competition with FXa for PL binding sites (Noordermeer et al ., 2021), actions which may account for the higher prevalence of LA described in patients with COVID-19 (Taha and Samavati, 2021).…”

Insights into origins and specificities of autoantibodies in systemic sclerosis

“…Downstream of the initial breach of tolerance, B cells coordinate the autoimmune response as antigen-presenting cells and as producers of autoantibodies, and recent work explores alterations in the signaling profiles and regulatory capacity of multiple B cell subsets [26 ▪▪ ,30,31 ▪ ]. Finally, newly-discovered autoantibodies may have predictive value or be involved in disease pathogenesis [35,36,43–53]. SSc, systemic sclerosis.…”