Interleukin-1 cytokines, inflammasomes, NOD-signalosomes and autoinflammation

The understanding of the genetic and immunological basis of human periodic fever syndromes, in particular cryopyrin-associated periodic syndromes (CAPS), has led to important new insights into the pathogenesis of monogenic and complex interleukin-1beta-associated autoinflammatory diseases. Currently the focus of attention is on the nucleotide-binding oligomerization domain (NOD)-like receptors (NLR), which take part in the regulation of the synthesis and maturation of cytokines in the IL-1 families, NOD-signalosomes and inflammasome

The versatility of the CD1 lipid antigen presentation pathway

The family of non-classical MHC class-I like CD1 molecules has an emerging role in human disease. Group 1 CD1 includes CD1a, CD1b, and CD1c which function to display lipids on the cell surface of antigen presenting cells for direct recognition by T cells. The recent advent of CD1 tetramers and the identification of novel lipid ligands has contributed towards the increasing number of CD1 restricted T cell clones captured. These advances have helped to identify novel donor unrestricted and semi-invariant T cell populations in humans and new mechanisms of T cell recognition. However, while there is opportunity to design broadly acting lipids and harness the therapeutic potential of conserved T cells, knowledge of their role in health and disease is lacking. We briefly summarise the current evidence implicating group 1 CD1 molecules in infection, cancer and autoimmunity and show that although CD1 are not as diverse as MHC, recent discoveries highlight their versatility as they exhibit intricate mechanisms of antigen presentation

Multidimensional phenotypes of asthma

Introduction and Objectives Asthma is a complex disease involving many cell types including CD4+ and CD8+ T cells, eosinophils, basophils and mast cells, and their soluble mediators. Poor understanding of disease heterogeneity and mechanisms underlying distinct clinico-pathological endotypes limits progress. <br/

Nasal carriage of Staphylococcus aureus and endonasal activity in Wegener’s granulomatosis as compared to rheumatoid arthritis and chronic rhinosinusitis with nasal polyps

Objectives: nasal colonisation with Staphylococcus aureus (S. aureus) has been implicated in Wegener`s granulomatosis (WG) disease activity. In this study, the frequency of nasal colonisation with S. aureus in WG was compared to healthy and disease control groups for the first time. Moreover, endonasal activity was correlated to colonisation.Patients and methods: nasal carriage of S. aureus of a well-defined group of 89 patients with WG was compared to 40 patients with chronic rhinosinusitis with nasal polyps (CRS), 35 patients with rheumatoid arthritis (RA), 50 hospital staff members and 25 subjects without regular hospital contact and correlation analysis of nasal carriage and endonasal activity of WG was performed. Results: WG patients showed significantly higher rates (72%) of nasal colonisation with S. aureus compared to CRS patients (28%) and healthy subjects without regular hospital contact (25%, 95%-CI), but not to RA patients (46%) and hospital staff members (58%). WG patients with nasal carriage of S. aureus had significantly higher endoscopically proven endonasal activity (p=0.01), significantly more often first manifestation of WG in the upper respiratory tract (p=0.02) and higher relapse-rates (p=0.052) than WG patients without such carriage. Conclusions: endonasal activity in WG is associated with higher nasal S. aureus colonisation rates and subsequent higher relapse rates. The higher frequency of S. aureus colonisation could be a consequence of a recently shown mucosal barrier defect in WG and facilitate chronic inflammation and granuloma formation in the upper respiratory tract