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 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. 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 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. 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.(AU)

Prevalencia de anticuerpos antifosfolípidos y anti anexina V en pacientes dializados de Bahía Blanca / Prevalence of antiphospholipid antibodies and anti anexin V in dialysis patients in Bahía Blanca / Prevalência de anticorpos antifosfolípides e anti anexina V em pacientes em diálise em Bahía Blanca

En los pacientes hemodializados son frecuentes las oclusiones de los accesos vasculares por una diálisis insuficiente y en un bajo porcentaje por un estado hipercoagulable desencadenado por anticuerpos dirigidos contra determinados componentes fosfolipídicos. El objetivo del trabajo fue evaluar la prevalencia de estos autoanticuerpos (APL) y del marcador anti anexina V en 79 pacientes en plan de hemodiálisis y en 66 donantes de sangre de la ciudad de Bahía Blanca. Para la detección del anticoagulante lúpico (AL) se realizaron estudios coagulométricos básicos, pruebas de detección, corrección con mezclas con plasma normal y ensayos confirmatorios con lisados plaquetarios. En paralelo, se efectuaron ensayos inmunológicos séricos: anticuerpos anticardiolipinas (ACL) IgM/IgG, anticuerpos anti β2 Glicoproteina I (aβ2GPI) IgM/IgG y anticuerpos anti anexina V IgM/IgG. Para estimar las diferencias se realizó el test de Fisher con una significancia del 5%. No se detectó anticoagulante AL en ninguna de las dos poblaciones. La prevalencia de los ACL IgG fue mayor en los dializados que en los dadores (31,6% vs. 12,1%, p: 0,0056); la correspondiente a las antiβ2 GPI fue similar (2,5% en dializados vs. 7,6% en dadores, p: 0,2458), mientras que la correspondiente a la anti anexina V IgG resultó mayor en dializados (16,4% vs. 4,5%, p: 0,0316). Los resultados obtenidos sugieren la importancia de monitorear la presencia de anticuerpos antifosfolípidos y anti anexina V previo al ingreso de un plan de diálisis para prevenir eventos trombóticos.

In hemodialysis patients, occlusions of vascular access are frequent due to insufficient dialysis and in a low percentage, due to a hypercoagulable state triggered by antibodies directed against certain phospholipid components. The objective of this work was to evaluate the prevalence of these autoantibodies (APL) and the anti-annexin V marker in 79 patients undergoing hemodialysis and in 66 blood donors in the city of Bahía Blanca. For the detection of lupus anticoagulant (LA), basic coagulometric studies, detection tests, correction with mixtures with normal plasma and confirmatory tests with platelet lysates were performed. In parallel, serum immunological assays were performed: IgM/IgG anticardiolipin antibodies (ACL), IgM/IgG anti-β2 glycoprotein I (aβ2GPI) antibodies and IgM/IgG anti-annexin V antibodies. To estimate the differences, a Fisher test with a significance of 5% was performed. Lupus anticoagulant (LA) was not detected in any of the two populations. The prevalence of IgG ACL was higher in the dialysate than in the donors (31.6% vs. 12.1%, p: 0.0056); the corresponding antiβ2GPI was similar (2.5% dialysate vs. 7.6% donors, p: 0.2458), while the corresponding anti-Annexin V IgG was higher in dialysate (16.4% vs. 4.5%, p: 0.0316). The results obtained suggest the importance of monitoring the presence of antiphospholipid and anti-annexin V antibodies prior to entry to a dialysis plan to prevent thrombotic events.

Em pacientes hemodialisados são frequentes as oclusões dos acessos vasculares devido a uma diálise insuficiente e, um percentual baixo, a um estado de hipercoagulabilidade desencadeado por anticorpos dirigidos contra determinados componentes dos fosfolípidos. O objetivo do trabalho foi avaliar a prevalência desses autoanticorpos (APL) e do marcador anti Anexina V em 79 pacientes em plano de hemodiálise e em 66 doadores de sangue da cidade de Bahía Blanca. Para a detecção do anticoagulante lúpico (AL) foram realizados estudos coagulométricos básicos, testes de detecção, correção com misturas com plasma normal e ensaios de confirmação com lisados de plaquetas. Em paralelo se realizaram ensaios imunológicos séricos: anticorpos anticardiolipinas (ACL) a IgM/IgG, anticorpos anti β 2 GlicoproteinaI (aβ 2GPI) IgM/IgG e anticorpos anti Anexina V IgM/IgG. Para estimar as diferenças foi realizado o teste de Fisher com uma significância de 5%. Não foi detectado anticoagulante AL em qualquer uma das duas populações. A prevalência de ACL IgG foi maior nos dialisados que nos doadores (31,6% vs. 12,1%, p: 0,0056); a correspondente às anti β 2GPI foi semelhante (2,5% em dialisados vs. 7,6% em doadores, p: 0,2458), enquanto que o correspondente à anti Anexina V IgG foi maior em dialisados (16,4% vs. 4.5 %, p: 0,0316). Os resultados obtidos sugerem a importância de monitorar a presença de anticorpos antifosfolipídios e anti Anexina V antes de entrar em um plano de diálise para prevenção de eventos trombóticos.