Autoinflammation and autoimmunity: pathogenic, clinical, diagnostic and therapeutic aspects.

T he third Israel-Italy Meeting on Advances in Autoimmunity and Rheumatology, organized by Professors Elias Toubi, Roberto Perricone and Yehuda Shoenfeld, has arrived. In the delightful setting of the Zabludowicz Center for Autoimmune Diseases at Sheba Medical Center, Tel Hashomer (Tel Aviv), physicians from Israel and Italy will share their expertise in several fields of Immunology and Rheumatology. An area that has gained relevance in recent years is Autoinflammatory Diseases. Giat and Lidar [1] present a paper on cryopyrin-associated periodic syndrome, a rare, autosomal dominant, autoinflammatory disorder associated with mutations in the NLRP3 gene. This condition results from an over-activation of the inflammosome, which leads to the secretion of interleukin (IL)-1β and IL-18, leading to chronic or recurrent systemic inflammation. The clinical manifestations may involve the skin, muscles, skeleton, joints, eyes and central nervous system (CNS), as well as progressive hearing loss. Although historically separated as three different syndromes – familial cold autoinflammatory syndrome (FCAS, also known as familial cold urticarial syndrome, FCU), Muckle-Wells syndrome (MWS), and neonatal onset multisystem inflammatory disorder (NOMID, also known as chronic infantile neurological cutaneous and articular syndrome, CINCA) – today the common genetic basis, etiopathogenetic mechanisms, and treatment suggest that they may represent the spectrum of a unique syndrome. While anti-IL-1 agents, such as anakinra, rilonacept and canakinumab, are the mainstay of therapy in the cryopyrin-associated periodic syndrome, other treatments are currently under investigation. In this context, Di Gangi et al. [2] evaluate the potential usefulness of adalimumab, an anti-tumor necrosis factor (TNF) agent, in another autoinflammatory disease: hyper-immunoglobulin D syndrome (HIDS). This is an autosomal recessive syndrome caused by specific mutations in the mevalonate kinase gene. Its main clinical feature is recurrent inflammatory attacks. Since unstimulated peripheral blood monocytes (PBMCs) from patients with inactive HIDS produce a complex network of inflammatory cytokines and undergo decreased apoptosis, the TNFα monoclonal antibodies, which indeed are able to induce apoptosis of lymphocytes, may be a valid therapeutic option. Further studies are warranted. An interesting approach to treat autoinflammatory disorders is described by Bashi et al. [3]. Starting from the assumption that the aim of helminths is to survive in the host, thus inducing a tolerance scenario, and that their eradication is linked to the increase of autoimmune conditions in certain countries, helminth conjugates and ova may be a promising treatment for inflammatory bowel disease. Cohen [4] proposes a shift in paradigm from a global suppression of the immune system, as we witness today, to a molecularly driven language of regulation. It was shown that the administration of a self-peptide to patients with new-onset Type 1 diabetes mellitus (T1D) could significantly arrest the autoimmune destruction of residual beta cells and enhance metabolic control of their diabetes. Cohen suggests that such peptides belong to the Immunological Homunculus; consequently, these self-antigens may function as immune modulators allowing such an apparently controversial result. Galeazzi et al. [5] present another therapeutic strategy based on the selective delivery of an immunoregulatory cytokine to the sites of inflammatory disease. This newly developed treatment, Dekavil, an ‘armed antibody’, consists of the human F8 antibody (specific to the EDA domain of fibronectin, a marker of angiogenesis) fused to the anti-inflammatory cytokine interleukin-1. The interesting feature is its structure, which allows the delivery and accumulation of the lL-10 cytokine at the sites of disease. A phase Ib clinical trial with initial signs of therapeutic benefit is currently underway in patients with rheumatoid arthritis (RA). autoimmunity, autoantibodies, autoimmune/inflammatory syndrome induced by adjuvants (ASIA), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), helminths, psoriatic arthritis (PsA), multiple sclerosis (MA), Type 1 diabetes mellitus, anti-Saccharomyces cerevisiae antibodies (ASCA), ferritin