Multiple sclerosis: Association of gelatinase B/matrix metalloproteinase-9 with risk and clinical course the disease

Background: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and axonal degeneration of the central nervous system and a leading cause of disability in young adults. The matrix metalloproteinases in general and specially gelatinase B/metalloproteinase-9 (MMP-9) plays a role in the pathogenesis of multiple sclerosis. Objective: To investigate the presence of the MMP-9 1562 C/T polymorphism in a Portuguese population of MS patients and assess its impact in susceptibility and course of the disease. The relation of MMP-9 serum levels with the polymorphism and with clinical and therapeutic factors will also be assessed. Methods: Our study included 355 Caucasian individuals distributed as MS patients (n=169) and controls (n=186). Samples were genotyped for 1562 C/T polymorphism by PCR-RFLP analysis. MMP-9 concentration in serum was analyzed using a commercially available enzyme-linked immunosorbent assay. Results: A significant increase in T-allele frequency was found in female MS patients, but not in the total patient population. No association between the presence of the polymorphism and disease progression was found. MMP-9 serum concentrations were increased in patients, and although not influenced by the 1562 C/T polymorphism, were modified by INF-beta therapy. Conclusion: Although we did not find an association of this polymorphism with disease susceptibility or prognosis, MMP-9 appears to be a good therapeutic response marker for multiple sclerosis.Portuguese Foundation for Science and Technology (FCT) through SFRH/PROTEC/67690/2010info:eu-repo/semantics/publishedVersio

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc

Therapeutic failure in American cutaneous leishmaniasis is associated with gelatinase activity and cytokine expression

Cutaneous lesions caused by Leishmania braziliensis infection occasionally heal spontaneously, but with antimonials therapy heal rapidly in approximately 3 weeks. However, about 15% of the cases require several courses of therapy. Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that have been implicated in other chronic cutaneous diseases and skin re-epithelialization. These enzymes are controlled by their natural inhibitors [tissue inhibitors of metalloproteinase (TIMPs)] and by some cytokines. Uncontrolled gelatinase activity may result in intense tissue degradation and, consequently, poorly healing wounds. The present study correlates gelatinase activity to therapeutic failure of cutaneous leishmaniasis (CL) lesions. Our results demonstrate an association between gelatinase activity and increased numbers of cells making interferon (IFN)-γ, interleukin (IL)-10 and transforming growth factor (TGF)-β in lesions from poor responders. Conversely, high levels of MMP-2 mRNA and enhanced MMP-2 : TIMP-2 ratios were associated with a satisfactory response to antimonials treatment. Additionally, high gelatinolytic activity was found in the wound beds, necrotic areas in the dermis and within some granulomatous infiltrates. These results indicate the importance of gelatinase activity in the skin lesions caused by CL. Thus, we hypothesize that the immune response profile may be responsible for the gelatinase activity pattern and may ultimately influence the persistence or cure of CL lesions