O R I G I N a L a Rt I C L E Hereditary Auto-inflammatory Disorders and Biologics

The term auto-inflammatory disorders has been coined to describe a group of conditions characterized by spontaneously relapsing and remitting bouts of systemic inflammation without apparent involvement of antigen-specific T cells or significant production of auto-antibodies. The hereditary periodic fever syndromes are considered as the prototypic auto-inflammatory diseases, and genetic studies have yielded important new insights into innate immunity. DNA analysis has greatly enhanced the clinical characterization of these conditions, and elucidation of their molecular aetiopathogenesis has suggested that therapies may be aimed at specific targets within the immune cascade. The availability of biologic response modifiers such as inhibitors of tumour necrosis factor (TNF) and interleukin-1β has greatly improved the outlook for some of these disorders, although effective therapies remain elusive in patients with certain conditions, including hyperimmunoglobulinaemia-D with periodic fever syndrome (HIDS) and a proportion of those with TNF-receptor associated periodic syndrome (TRAPS). Indeed, outstanding challenges and the unique potential to further elucidate molecular mechanisms in innate immunity are illustrated by the dashed early hope that TNF blockade would be a panacea for TRAPS: not only is etanercept (Enbrel) ineffective in some cases, but there are anecdotal reports of this condition being greatly exacerbated by infliximab (Remicade). Dr. S.M. Churchman and Dr. L.D. Church provided equal contributions to this review. L. D. Church . S. M. Churchman . M. F. McDermott Academic Unit of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Epidemiology and Cancer Research, University of Leeds, Leeds, UK P. N. Hawkins National Amyloidosis Centre, Royal Free & University College Medical School, London, UK M. F. McDermott ()) Leeds Institute of Molecular Medicine, University of Leeds, St. James’s University Teaching Hospital, Beckett Street, Leeds, LS9 7TF, UK e-mail: [email protected] . Tel.: +44-113-3438641 . Fax: +44-113-3438702 Springer Semin Immun