Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).

Heart failure in a woman with SLE, anti-phospholipid syndrome and Fabry's disease.

We describe a female patient with systemic lupus erythematosus (SLE) also diagnosed with Fabry's disease and anti-phospholipid antibody syndrome (APS). SLE and Fabry's disease are both systemic diseases with variable clinical presentations. Recent studies have shown a relatively high incidence of late onset Fabry's disease in female heterozygous individuals, suggesting that this condition could be under-diagnosed. We discuss a possible association between SLE and Fabry's disease and consider the role of lipid abnormalities in the pathogenesis of SLE.

T-lymphocyte signalling in systemic lupus erythematosus: a lipid raft perspective.

In the last few years it has become clear that in cells of the immune system, specialized microdomains present in the plasma membrane, called lipid rafts, have been found to play a central role in regulating signalling by immune receptors. Recent studies have looked at whether lipid rafts may be connected to the abnormalities in signalling seen in T lymphocytes isolated from patients with systemic lupus erythematosus (SLE). These early findings show that in SLE T cells, the expression and protein composition of lipid rafts is different when compared with normal T cells. These results also demonstrate changes in the function and localization of critical signalling molecules such as the LCK tyrosine kinase and the CD45 tyrosine phosphatase.