Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation

In 1997, the first consensus guidelines for haematopoietic SCT (HSCT) in autoimmune diseases (ADs) were published, while an international coordinated clinical programme was launched. These guidelines provided broad principles for the field over the following decade and were accompanied by comprehensive data collection in the European Group for Blood and Marrow Transplantation (EBMT) AD Registry. Subsequently, retrospective analyses and prospective phase I/II studies generated evidence to support the feasibility, safety and efficacy of HSCT in several types of severe, treatment-resistant ADs, which became the basis for larger-scale phase II and III studies. In parallel, there has also been an era of immense progress in biological therapy in ADs. The aim of this document is to provide revised and updated guidelines for both the current application and future development of HSCT in ADs in relation to the benefits, risks and health economic considerations of other modern treatments. Patient safety considerations are central to guidance on patient selection and HSCT procedural aspects within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and EBMT accredited centres. A need for prospective interventional and non-interventional studies, where feasible, along with systematic data reporting, in accordance with EBMT policies and procedures, is emphasized

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Prevalence, predictors and outcome of vascular damage in systemic lupus erythematosus

Despite improved prognosis, patients with systemic lupus erythematosus (SLE) remain at increased risk for early death. Vascular events (VE) occur with increased frequency and contribute to premature death in SLE patients. As conventional cardiovascular risk factors do not fully explain this hazard, this study investigated the contribution of disease-specific features to VE development. Documented VE were classified as atherothrombotic, venous thrombotic, arterial thrombotic or tissue loss inducing vasculitis during a mean follow-up of nearly 12 years in the Tromsø Lupus cohort ( n = 158). The impact of disease-specific factors (organ manifestations, laboratory findings, drug treatment, weighted average SLE Disease Activity Index (WAS) and cumulative Damage Index) was assessed by odds ratios for VE in multivariate analysis. A total of 41 patients (26%) developed VE, and atherothrombotic events were most common (73%). Overall, VE prevalence was 3.5/100 patient years, and VE risk increased linearly over time, reaching 35% after 20 years. WAS scores &gt;3 increased, and use of hydroxychloroquine and antihypertensive medication reduced overall VE risk. Age &gt;40 years was the main risk factor for atherothrombotic events. VE nearly quadrupled the risk of death. VE occurred in 26% of SLE patients, predominantly as atherothrombotic disease. VE prevalence increased linearly over time leading to a four-fold risk of mortality. Strategies for reducing disease activity, including treatment with antimalarials and antihypertensive drugs, are most likely to reduce the risk associated with VE in SLE. </jats:p

Circulating interferon-α2 levels are increased in the majority of patients with systemic lupus erythematosus and are associated with disease activity and multiple cytokine activation

Mutations in interferon (IFN) regulatory factor genes and the biological activity of type I IFN on expression of specific genes that are induced by IFN have been associated with various aspects of systemic lupus erythematosus (SLE). Circulating levels of IFN-α in SLE has not been extensively studied because of limited sensitivity of available ELISA assays. We performed a cross-sectional case-control study where circulating levels of IFN-α2 were measured by a highly sensitive, solution phase multiplex magnetized bead assay and investigated the relation of IFN-α2 with autoantibody profiles, clinical disease activity and levels of inflammatory cytokines in SLE patients ( n = 87). Cytokine levels were determined on stored sera aliquots with cut-off levels determined by the geometric mean + 2SD in healthy controls ( n = 27). IFN-α2 levels were increased in 64% of SLE patients, who displayed more renal disease and higher disease activity ( p = 0.06) and had a significantly higher sum of activated cytokines (median 4.5, range 7) compared to patients with normal IFN-α2 (median one, range 3; p &lt; 0.001). Solution phase micro-bead assay thus identified increased IFN-α2 levels in two-thirds of SLE patients with longstanding disease. The association with clinical disease and activation of multiple inflammatory cytokines supports a role for IFN-α2 in disease perpetuation in a large subset of SLE patients. </jats:p