Blood to skin recirculation of CD4+ memory T cells associates with cutaneous and systemic manifestations of psoriatic 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.

A role for CCR5(+)CD4 T cells in cutaneous psoriasis and for CD103(+) CCR4(+) CD8 Teff cells in the associated systemic inflammation.

Recent results have identified critical components of the T cell response involved in the initiation and amplification phases of psoriasis. However the link between T cell responses arising in the skin and the systemic inflammation associated with severe psoriasis is largely unknown. We hypothesized that specific subsets of memory T cells recirculating from the skin could play a role. We therefore dissected the circulating memory T cell compartment in patients by analyzing the TCM, TEM and Teff phenotype, the pattern of CCR4 and CCR5 chemokine receptor expression and the expression of the tissue homing molecule CD103. For each subset we calculated the correlation with the Psoriasis Area and Severity Index (PASI) and with the extent of systemic inflammation measured as serum level of the prototypic short pentraxin, C reactive protein (CRP). Validation was performed by comparison with gene expression data in psoriatic plaques. We found that circulating CD103(+)CCR4(+)CCR5(+) and CCR4(+)CCR6(-) CD8(+) Teff cells, were highly correlated with CRP levels as well as with the validated index PASI, reflecting a link between skin involvement and systemic inflammation in patients with severe psoriasis. In addition we observed a contraction of circulating CCR5(+) T cells in psoriasis patients, with a highly significant inverse correlation between CCR5(+)CD4 T cells and the PASI score. Increased expression of CCR5 and CCL5 genes in psoriatic skin lesions was consistent with an accumulation of CCR5(+) cells in psoriatic plaques indicating a role for CCR5/CCL5 axis in disease pathogenesis.

Dual role of anti-TNF therapy: enhancement of TCR-mediated T cell activation in peripheral blood and inhibition of inflammation in target tissues.

The impact of anti-TNF therapy on systemic immune responses in patients has not been clearly defined. Here, we examined Th1/Th2/Th17 cytokine expression, activation and proliferation of peripheral T cells from patients with psoriasis and inflammatory bowel disease before and during anti-TNF therapy. In parallel, we calculated the correlation with the clinical response and we monitored cytokine expression in biopsies from inflamed tissues. We evidenced a dual role of TNF-blockade. In peripheral blood, it increased the expression of cytokines such as IL-17, IL-10, and IFN-γ, and enhanced the expression of activation markers and the proliferative response of CD4 T cells to TCR stimulation. By contrast, in biopsies from target tissues, TNF-blockade diminished the expression of Th17/Th1 cytokine and early inflammatory genes. Importantly, the enhanced T cell responses to TCR-stimulation did not impair the clinical response to the therapy and, in responder patients, occurred with the concomitant down-regulation of inflammatory genes in the target tissues.

Metal sensitivity in patients with orthopaedic implants: a prospective study.

BACKGROUND: Sensitization to orthopaedic implant materials is an unpredictable event that might affect implant performance. OBJECTIVES: In candidates for hip or knee joint prosthesis implantation, to evaluate preoperative assessments for identifying patients with metal sensitivity, to determine the percentage of patients who developed metal sensitivity at 1 year after prosthesis implantation, and to examine the clinical relevance of patch tests and lymphocyte transformation tests (LTT-MELISA®) for the evaluation of metal sensitization. PATIENTS AND METHODS: A total of 100 patients referred for total hip or total knee arthroplasty were assessed preoperatively and then at 1 year post-implantation by means of patch tests with the metals present in the implant alloys. In a pilot study, 20 patients also underwent both patch testing and a lymphocyte transformation test (LTT-MELISA®) for the same metals. RESULTS: Only 72 of 100 patients were patch tested both before and after surgery, and 12 of 20 also underwent LTT-MELISA® before and after surgery. Of 31/100 patients with an apparent history of nickel sensitivity determined during preoperative assessment of subjects, 12 tested negative on both tests, and 4 with a negative history of nickel sensitivity tested positive. One year post-implantation (72 patients), 5 patients who had initially tested negative for a metal allergy became positive for at least one or more metal constituents of the prosthesis on at least one or the other test. CONCLUSIONS: Given the discrepancies between the information obtained while taking patient histories and test results, preoperative history-taking alone appears to be insufficient for identifying patients with metal sensitivity. Moreover, the increase in the percentage of patients who tested positive for metal sensitivity 1 year post-implantation suggests the possibility of prosthesis-induced sensitization. Therefore, objective determination of metal sensitivity at preoperative assessment should be considered in planning arthroplasty intervention, as it would help the surgeon in selecting the most appropriate prosthesis for the patient and could benefit implant performance.

A controlled study of comparative efficacy of oral retinoids and topical betamethasone/salicylic acid for chronic hyperkeratotic palmoplantar dermatitis.

BACKGROUND: Chronic hyperkeratotic dermatitis of the palms and soles represents a severe multi-etiological problem, too often faced with ineffective or tedious topical remedies. METHODS: A single-blind, matched-sample design investigation was carried out of 42 patients with chronic hyperkeratotic palmoplantar dermatitis, who were administered acitretin 25-50 mg/day for 1 month, which was controlled versus a conventional topical treatment (betamethasone/salicylic acid ointment). Therapeutic improvement was expressed with the reduction of severity score (expressed on a 0-10 scale). RESULTS: Acitretin was significantly better than the conventional treatment after 30 days (two sided p<0.0001). Moreover, improvement significantly persisted 5 months after suspension of acitretin (p<0.0001), while this was not the case after suspension of the control treatment (p=0.3019). Lesions improved more rapidly with acitretin than with the control treatment (p<0.0002). Some cases of loss of sensitization in patch-test-positive patients were observed. Side effects were minimal or absent, and patients expressed overtly their preference for acitretin treatment. CONCLUSION: After evaluating the former literature, the risks and the benefits, as well as the overt superiority of retinoid treatment, the authors conclude that acitretin should be considered a first choice treatment for this fastidious condition.