Summary Background Rare highly penetrant gain of function mutations in caspase recruitment domain family, member 14 (CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. Objectives To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and expand knowledge of CARD14 variants in the European population. Methods CARD14 coding exons were re-sequenced in psoriasis cases and controls from Tunisia and Europe including included sixteen European cases with generalized pustular psoriasis (GPP). Novel variants seen in cases were evaluated for their effect upon NF-kb signalling. Results Rare variants in CARD14 were significantly enriched in Tunisian cases compared to controls. Three were collectively found in 5% of Tunisian cases and all affected the N terminal region of the protein harbouring its CARD or coiled-coil domain. These variants were: c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-kb activity in a similar manner to previously described psoriasis-associated mutations. p.Arg69Trp led to seven fold down-regulation of NF-kb activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9 which encodes part of the coiled-coil domain. No GPP cases harboured an IL36RN mutation, but one out of 16 GPP cases with a family history of PV harboured a c.1805C>T (p.Ser602Leu) mutation. Conclusions These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations.

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Our data strongly support that the changes of thyroid hormones may be influenced by adiposity and its metabolic consequences, such as insulin resistance. This relationship can be explained by a cross talk between adipose tissue release and thyroid function. Nevertheless, metformin treatment seems to affect thyroid function in diabetic patients by maintaining plasma thyrotropin levels to subnormal levels.

Antinuclear antibodies (ANAs) are significant biomarkers in the diagnosis of autoimmune diseases in humans, done by mean of Indirect ImmunoFluorescence (IIF) method, and performed by analyzing patterns and fluorescence intensity. This paper introduces the AIDA Project (autoimmunity: diagnosis assisted by computer) developed in the framework of an Italy-Tunisia cross-border cooperation and its preliminary results. A database of interpreted IIF images is being collected through the exchange of images and double reporting and a Gold Standard database, containing around 1000 double reported images, has been settled. The Gold Standard database is used for optimization of a CAD (Computer Aided Detection) solution and for the assessment of its added value, in order to be applied along with an Immunologist as a second Reader in detection of autoantibodies. This CAD system is able to identify on IIF images the fluorescence intensity and the fluorescence pattern. Preliminary results show that CAD, used as second Reader, appeared to perform better than Junior Immunologists and hence may significantly improve their efficacy; compared with two Junior Immunologists, the CAD system showed higher Intensity Accuracy (85,5% versus 66,0% and 66,0%), higher Patterns Accuracy (79,3% versus 48,0% and 66,2%), and higher Mean Class Accuracy (79,4% versus 56,7% and 64.2%).