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1.  Biological markers in the etiology of psoriasis: Targeted treatment options 
Biologics : Targets & Therapy  2007;1(1):11-18.
Psoriasis is a common chronic and disabling inflammatory disease that has an enormous physical, functional and psychosocial impact on patients’ quality of life. To date several conventional therapies are available for the treatment of this condition (eg, cyclosporine, methotrexate, retinoids, and psoralen plus ultraviolet A) which, although providing clinical response, do not maintain long-lasting disease remission and at times show poor tolerability with potential toxicity thus limiting their use. A challenge in psoriasis management is to utilize precociously an adequate therapy and to achieve effective and safe maintenance of its clearance by improving both skin and joint manifestations as well as to prevent joint destruction and disability. Recent improvement in the knowledge of the pathogenesis of this disease was fundamental for the development of novel targeted treatment options that may be effective, safer and well tolerated on long-term administration periods, thus improving patient’s quality of life. These novel agents, which are called “biologics”, target specifically tumor necrosis factor-α (infliximab, etanercept and adalimumab) or T cells (alefacept and efalizumab).
PMCID: PMC2721342  PMID: 19707344
psoriasis; biologics; anti-TNF-α; anti-T cells
2.  Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of patients with psoriatic arthritis after therapy with anti-TNF-α 
Background
Inflammation represents an early and key event in the development of both the cutaneous psoriasis and psoriatic arthritis. Compelling evidences indicate that the production of TNF-α plays a central role in psoriasis by sustaining the inflammatory process in the skin as well as in the joints. Among the multiple effects produced by TNF-α on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammatory arthritis which acts as an angiogenesis promoting factor, might represent a key mechanism in the pathogenesis of the disease. Aims of the present study were to investigate a) the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients; b) the association of MMP-9 with the activity of the disease; c) the relationship between MMP-9 and TNF-α production.
Methods
Eleven psoriatic patients, clinically presenting joint symptoms associated to the cutaneous disease, were included in a therapeutic protocol based on the administration of anti-TNF-α monoclonal antibody (Infliximab). Sera and skin biopsies were collected before treatment and after 6 weeks of therapy. Tissues were kept in short term cultures and production soluble mediators such as TNF-α, MMP-9, MMP-2, VEGF and E-Selectin, which include angiogenic molecules associated to the development of plaque psoriasis, were measured in the culture supernatants by immunoenzymatic assays (ng/ml or pg/ml per mg of tissue). MMP-9 concentrations were also measured in the sera. The cutaneous activity of disease was evaluated by the Psoriasis Area and Severity Index (PASI).
Results
Clinical and laboratory assessment indicated that all but one patients had a significant improvement of the PASI score after three months of therapy. The clinical amelioration was associated to a significant decrease of MMP-9 (P = 0.017), TNF-α (P = 0.005) and E-selectin (P = 0.018) levels, spontaneously released by lesional biopsies before and after therapy. In addition, significant correlations were found between the PASI measurements and TNF-α (r2 = 0.33, P = 0.005), MMP-9 (r2 = 0.25, P = 0.017), E-selectin (r2 = 0.24, P = 0.018) production. MMP-9 levels were significantly correlated with those of TNF-α (r2 = 0.30, P = 0.008). A significant decrease of MMP-9 in the sera, associated to the clinical improvement was also found.
Conclusion
Our findings show the existence of a direct relationship between MMP-9 and TNF-α production strongly suggesting that MMP-9 may play a key role in the skin inflammatory process in psoriasis.
doi:10.1186/1740-2557-3-5
PMCID: PMC1601955  PMID: 17022813

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