Cutaneous lymphocyte-associated antigen as a novel predictive marker of TNF-alpha inhibitor biological therapy in psoriasis.

A considerable number of patients with psoriasis show secondary resistance during long-term TNF-alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte-associated antigen (CLA) was investigated. Thirty-eight severe patients with psoriasis were treated for a 24-week-long study period. Clinical responsiveness (PASI) and changes in flow cytometry-measured peripheral lymphocyte CLA expression (week 0-2-6) were statistically analysed. Regarding 24-week-long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearson's correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF-alpha inhibitor therapy in psoriasis.

Impact of effective tumor necrosis factor-alfa inhibitor treatment on arterial intima-media thickness in psoriasis: results of a pilot study.

BACKGROUND: Psoriasis is associated with higher incidence of atherosclerotic comorbidities. Sustained arterial wall inflammation mediated by common cytokines of psoriasis and atherogenesis precedes atherosclerotic plaque development. Increased intima-media thickness (IMT) is an accepted indicator of subclinical atherosclerosis and has been reported in severe psoriasis. OBJECTIVE: This pilot study aimed to clarify whether effective long-term tumor necrosis factor-alfa inhibition decreases IMT in psoriasis. METHODS: In 16 patients with severe psoriasis, the Psoriasis Area and Severity Index score was calculated before therapy (etanercept, infliximab, adalimumab) and after 6-month treatment. Simultaneously, carotid and brachial IMT was measured by high-resolution, B-mode ultrasonography. Difference between initial and 6-month IMT values was determined for monitored arteries collectively and separately in carotid and brachial arteries. RESULTS: All of 16 patients achieved Psoriasis Area and Severity Index 75, and 14 of 16 achieved Psoriasis Area and Severity Index 90 improvement. In the group of patients without initial calcified atherosclerotic plaques (13 of 16) significant IMT decrease was detected when arteries were measured collectively (P = .0002). Initial and follow-up data differed significantly also at individual analysis of carotid (P = .011) and brachial (P = .006) arteries. Eleven of 13 patients had initial carotid IMT exceeding age-adjusted normal values. The other group (3 of 16) with initial manifest plaques showed increasing IMT tendency. Their baseline ultrasonography revealed carotid IMT above the upper limit of healthy adults' age-adjusted values. LIMITATIONS: Study limitation involves small patient numbers, self-controlled study design, and lack of patients' stratification according to common cardiovascular risk factors. CONCLUSION: In our pilot study effective tumor necrosis factor-alfa inhibition was found to decrease IMT in psoriatic patients without irreversible atherosclerotic plaques. Further analysis is recommended to confirm and complete our primary observations.

Tissue-specific homing of immune cells in malignant skin tumors.

Tissue-specific migration of immune cells involved both in physiological and pathological immune responses is a current research subject for medical science. Several homing molecules have been identified orchestrating extravasation of immune cells to certain peripheral non-lymphoid tissues such as gut, lung and skin. Regarding lymphocyte homing to skin, the first-line defense of human body cutaneous lymphocyte associated antigen (CLA) and a group of chemokine-chemokine receptor pairs are considered to be of crucial importance. The aim of the present review is to summarize existing knowledge about skin- and tumor-specific migration of immune cells playing a major pathogenetic role in host immune responses induced by non-lymphoid malignant skin tumors as well as in the development of primary cutaneous T-cell lymphomas (CTCL). Melanoma malignum, squamous and basal cell carcinoma evoke host immune responses and consequently a subset of reactive immune cells is recruited to site of the tumor. Regarding migratory process and exact functional role of these cells a growing number of data is available in literature. On the other hand tissue-specific immune cell homing is regarded as a key process in the pathogenesis of CTCL where malignant T-lymphocytes can be found in circulation and symptomatic skin. Hereby homing mechanism of malignant T-cells in mycosis fungoides and Sézary-syndrome as separate clinical entities of CTCL is discussed. A precise insight into the molecular background of skin- and tumor-specific immune cell migration can contribute to developing efficient vaccine therapies in non-lymphoid malignant skin tumors and beneficial treatment modalities in CTCL.