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The SAP4PRISMA is a four year research project which aims at developing algorithms and products for the future PRISMA mission. The project started on May 2010 and is now entering his full activities as the ”PRISMA like” data set has been defined and the test areas were selected. The paper describes the main project objectives and the activities realized in the first 9 months of the project.

The aim of this study is to identify subsets of T cells differentially represented in the circulation of patients with psoriatic arthritis and to evaluate the possibility that they can recirculate between peripheral blood and the inflamed joints. We analyzed the phenotype and cytokine expression in circulating CD8+ and CD4+ T cells in 69 subjects: 28 with cutaneous psoriasis, 15 patients with psoriatic arthritis, and 26 healthy subjects. In the circulation, the percentage of each subset was compared among the groups and correlation was calculated with the serum concentration of C-reactive protein. To investigate the migration of T cells towards the inflamed joints, we performed a transwell migration assay towards patient serum and synovial fluid. In selected patients we analyzed in parallel T cells from peripheral blood and from synovial fluid. In the circulation, we found increased percentage of CD8+ CCR6+ T cell effectors expressing CD69 and of IL-17-producing T cells in patients with psoriatic arthritis. CD8+ effector/effector memory T cells showed increased migration towards synovial fluid. Finally, in synovial fluid we found accumulation of CXCR3+ CD8+ T cells and CD69+ cells. CD4+ T cells in the two compartments shared many similarities with CD8+ T cells. The results indicate a role for memory T cell effectors in systemic and joint manifestations of psoriatic arthritis.

Fibromyalgia is one of the most important “rheumatic” disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1β, IL-6, and TNFα. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia.

(1) Background: In literature it is reported that 20&ndash, 30% of psoriatic patients evolve to psoriatic arthritis over time. Currently, no specific biochemical markers can either predict progression to psoriatic arthritis or response to therapies. This study aimed to identify osteoimmunological markers applicable to clinical practice, giving a quantitative tool for evaluating pathological status and, eventually, to provide prognostic support in diagnosis. (2) Methods: Soluble (serum) bone and cartilage markers were quantified in 50 patients with only psoriasis, 50 psoriatic patients with psoriatic arthritis, and 20 healthy controls by means of multiplex and enzyme-linked immunoassays. (3) Results: Differences in the concentrations of matrix metalloproteases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), receptor activator of nuclear factor kappa-B- ligand (RANK-L), procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTx-I), dickkopf-related protein 1 (DKK1), and sclerostin (SOST) distinguished healthy controls from psoriasis and psoriatic arthritis patients. We found that MMP2, MMP12, MMP13, TIMP2, and TIMP4 distinguished psoriasis from psoriatic arthritis patients undergoing a systemic treatment, with a good diagnostic accuracy (Area under the ROC Curve (AUC) &gt, 0.7). Then, chitinase-3-like protein 1 (CHI3L1) and MMP10 distinguished psoriasis from psoriatic arthritis not undergoing systemic therapy and, in the presence of onychopathy, MMP8 levels were higher in psoriasis than in psoriatic arthritis. However, in these latter cases, the diagnostic accuracy of the identified biomarkers was low (0.5 &lt, AUC &lt, 0.7). (4) Conclusions. By highlighting never exploited differences, the wide osteoimmunological biomarkers panel provides a novel clue to the development of diagnostic paths in psoriasis and psoriasis-associated arthropathic disease.

Blood to skin recirculation could play a role in the pathogenesis of psoriasis. To investigate this possibility we dissected the phenotype of circulating T cells in psoriasis patients, calculated the correlation the clinical parameters of the disease and performed a parallel bioinformatics analysis of gene expression data in psoriatic skin. We found that circulating CCR6+ CD4+ TEM and TEFF cells significantly correlated with systemic inflammation. Conversely, the percentage of CXCR3+ CD4+ TEM cells negatively correlated with the severity of the cutaneous disease. Importantly CLA+ CD4+ TCM cells expressing CCR6+ or CCR4+CXCR3+ negatively correlated with psoriasis severity suggesting recruitment to the skin compartment. This assumption was reinforced by gene expression data showing marked increase of CCR7 and CLA-encoding gene SELPLG expression in psoriatic skin and strong association of their expression. The data enlightens a role for CD4+ T cells trafficking between blood and skin in cutaneous and systemic manifestations of psoriasis.

Objective Adalimumab has proven effective in psoriasis; however, secondary failure may result from the drug9s immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients. Design Case–control, longitudinal. Setting Single centre. Participants Patient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab. Healthy subjects : (group V; n=15) never treated with immunosuppressants or biologicals. Interventions All groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months. Primary and secondary outcome measures Standard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISA-based measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα. Results The false-positive rate was 23% for adalimumab detection and 22% for anti-adalimumab antibodies in patients naive to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-time-point positivity in group III during follow-up) accounted for 33% of the total. The prevalence of anti-drug antibodies was highest (87%) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores. Conclusions High variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay9s usefulness. Accurate clinical evaluation is key to early identification of treatment failures.