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1.  Assessment of T Regulatory Cells and Expanded Profiling of Autoantibodies May Offer Novel Biomarkers for the Clinical Management of Systemic Sclerosis and Undifferentiated Connective Tissue Disease 
In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc) and undifferentiated connective tissue disease (UCTD), we have explored the setting of peripheral T regulatory (T reg) cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc) or diffuse (dcSSc) disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression.
doi:10.1155/2013/390563
PMCID: PMC3681301  PMID: 23818915
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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