Literature on Psoriatic Arthritis

Related ArticlesTherapeutic benefit of PDE4 inhibitors in inflammatory diseases.

Curr Opin Investig Drugs. 2007 May;8(5):364-72

Authors: Dastidar SG, Rajagopal D, Ray A

Intracellular levels of cyclic nuclec tides are closely regulated by distinct families of PD Es, which are responsible for the breakdown and degradation of cyclic nucleotides within cells. Type 4 PDEs have the potency to modulate the release of inflammatory mediators through cAMP-dependent and -independent mechanisms. Selective targeting of PDE4 is currently being investigated as a novel therapeutic approach in the treatment of inflammation-associated respiratory diseases such as asthma and COPD. The development of several PDE4 inhibitors, including roflumilast and cilomilast, reflects the success of this approach. In principle, therapeutic intervention of an inflammatory response by PDE4 inhibitors may be extended to other chronic inflammatory disease states such as psoriasis, rheumatoid arthritis and inflammatory bowel diseases (e.g., Crohns disease and ulcerative colitis). This retiiew explores the feasibility of PDE4 inhibitors as a promising alternative for therapeutic intervention in systemic inflammation and inflammation-based disease.

PMID: 17520865 [PubMed - indexed for MEDLINE]

]]>

Related ArticlesPharmacodynamic effects of the murine p75-Fc fusion protein in mice.

J Investig Dermatol Symp Proc. 2007 May;12(1):50-1

Authors: Hu YL, Kim HY, Kohno T, Khare SD

Overproduction of inflammatory mediators, such as tumor necrosis factor (TNF), is key to the development and maintenance of inflammatory processes. Etanercept is a soluble TNF receptor fusion protein used in the treatment of various chronic inflammatory diseases, including rheumatoid arthritis and psoriasis. This study investigated the effects of murine p75-Fc, a soluble TNF receptor protein, on TNF-induced IL-6 production in mice. Six groups of mice received either murine p75-Fc (0.15, 0.50, 1.5, 5, and 15 mg/kg) or phosphate-buffered saline. Three days later, mice were injected intravenously with 10 microg of murine TNF and blood samples were taken after 3 hours. Serum IL-6 and TNF were measured by ELISA. Mice treated with 5 and 15 mg/kg murine p75-Fc demonstrated complete inhibition of TNF-induced IL-6 production. Murine p75-Fc (1.5 mg/kg) resulted in a partial but significant reduction of TNF-induced IL-6 production. No TNF was detected in 5 and 15 mg/kg murine p75-Fc-treated mice, except one in the 5 mg/kg dose group. In conclusion, murine p75-Fc completely inhibits TNF-induced IL-6 production in mice.

PMID: 17502871 [PubMed - indexed for MEDLINE]

]]>

Related ArticlesConstruction and purification of the murine p75-murine IgG1 fusion protein.

J Investig Dermatol Symp Proc. 2007 May;12(1):48-9

Authors: Kim HY, Renshaw-Gegg LW, Balciunas AM, Kohno T

Etanercept (Amgen Inc, Thousand Oaks, CA) is a human soluble p75 tumor necrosis factor (TNF) receptor-human-IgG1 (hup75 TNFR-huIgG1) fusion protein used in the treatment of chronic inflammatory diseases in humans, including rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. To be able to study the effects of the soluble receptor fusion protein in mouse models, including those that mimic human granulomatous infections, a murine soluble p75-TNF receptor-murine IgG1 (murine p75-murine IgG1) fusion protein had to be constructed. This article discusses the generation, large-scale production, and purification of this molecule.

PMID: 17502870 [PubMed - indexed for MEDLINE]

]]>

Related ArticlesReactivation of latent tuberculosis by TNF blockade: the role of interferon gamma.

J Investig Dermatol Symp Proc. 2007 May;12(1):16-21

Authors: Wallis RS

Tumor necrosis factor (TNF) plays a pathogenic role in psoriasis and rheumatoid arthritis but is essential for host defenses against mycobacteria and other granulomatous pathogens. The risk of reactivation of latent Mycobacterium tuberculosis infection is significantly greater with the TNF monoclonal antibody infliximab than with the soluble TNF-receptor etanercept. We have examined the biologic basis of this difference using whole blood culture. Infliximab and adalimumab reduced the proportion of T buciclate-responsive cells by 70 and 50%, respectively, and suppressed antigen-induced IFN-gamma production by 70 and 64%. In contrast, etanercept produced no significant effect. The difference between infliximab and etanercept remained whether one compared equal or peak therapeutic drug concentrations, suggesting a relationship to mechanism of action rather than pharmacokinetics. Adalimumab and etanercept caused divergent, concentration dependent effects on control of intracellular growth of M. tuberculosis. None of the drugs induced significant levels of apoptosis or necrosis in monocytes or T cells, excluding T-cell death as a mechanism for suppression of antigen-induced responses. IL-10 production was equally suppressed by all three drugs, excluding excess IL-10 as a regulatory mechanism. The tuberculosis risk posed by infliximab may reflect its combined effects on TNF and IFNgamma.

PMID: 17502864 [PubMed - indexed for MEDLINE]

]]>

Related ArticlesEffects of etanercept are distinct from infliximab in modulating proinflammatory genes in activated human leukocytes.

J Investig Dermatol Symp Proc. 2007 May;12(1):9-15

Authors: Haider AS, Cardinale IR, Whynot JA, Krueger JG

Proinflammatory diseases like rheumatoid arthritis, Crohn’s disease, and psoriasis have been treated by the tumor necrosis factor (TNF) antagonists infliximab and etanercept with different degrees of success. Although these agents are widely used in humans, little is known about their mechanisms of action or why etanercept and infliximab have differences in clinical activity. In this study, we define leukocyte genes that are suppressed by etanercept within 24 hours of exposure. Compared to previous work with infliximab, fewer immune-related genes are suppressed by etanercept. Importantly, the range of genes suppressed by these alternative TNF inhibitors is only partially overlapping, suggesting each has unique immune modulating effects. In sharp contrast to etanercept, infliximab strongly suppresses genes associated with “Type 1″ immune responses (IFN-gamma and the IL-12-receptor beta 2 subunit), providing a clear mechanism for clinically relevant immune suppression.

PMID: 17502863 [PubMed - indexed for MEDLINE]

]]>

Related ArticlesDendritic cells in autoimmune diseases and neuroinflammatory disorders.

Front Biosci. 2007;12:4315-35

Authors: Manuel SL, Rahman S, Wigdahl B, Khan ZK, Jain P

Dendritic cells are the most potent antigen presenting cells and have long been recognized as key regulators of the immune system, linking both stimulatory and inhibitory components of normal immunity. While DCs are fully characterized with respect to primary and secondary immune responses, their unique role in coordinating central and peripheral tolerance is just emerging. It is increasingly evident that the failure of DCs ability to maintain tolerance can lead to autoimmune and/or inflammatory diseases. However, existing literature highlighting participation of DCs in several autoimmune phenomena is scattered and remains underappreciated. This review is a comprehensive account of current knowledge characterizing the role of DCs in various autoimmune diseases including psoriasis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, and diabetes. Additionally, it provides a rare description of DCs participation in various neuroinflammatory disorders including multiple sclerosis, HAM/TSP, Alzheimer disease and prion-associated diseases. Finally, a detailed description of the possible mechanisms of DC involvement in regulating immune response towards self versus non-self is discussed. Overall, the goal of this review is to establish DCs in the interface of tolerance and autoimmunity and generate a global interest in this field in order to exploit DC potential for the therapy of inflammatory diseases.

PMID: 17485377 [PubMed - indexed for MEDLINE]

]]>

Related ArticlesConsensus on a core set of domains for psoriatic arthritis.

J Rheumatol. 2007 May;34(5):1167-70

Authors: Gladman DD, Mease PJ, Strand V, Healy P, Helliwell PS, Fitzgerald O, Gottlieb AB, Krueger GG, Nash P, Ritchlin CT, Taylor W, Adebajo A, Braun J, Cauli A, Carneiro S, Choy E, Dijkmans B, Espinoza L, van der Heijde D, Husni E, Lubrano E, McGonagle D, Qureshi A, Soriano ER, Zochling J

A psoriatic arthritis (PsA) module was convened at OMERACT 8 in order to achieve consensus on the core domains that should be included in randomized controlled trials and longitudinal observational cohorts of subjects with PsA. Following a plenary session at which current status of measures used to assess PsA were reviewed, and discussion at breakout groups, the group achieved consensus on 6 core domains: peripheral joint activity, skin activity, pain, patient global assessment, physical function, and health-related quality of life. In addition the following domains were considered important but not mandatory: spinal disease, dactylitis, enthesitis, fatigue, nail disease, radiography, physician global assessment, and acute-phase reactants. A research agenda was proposed to include development and validation of instruments for the domains where none existed, and in particular further research was recommended for the following areas: magnetic resonance imaging and ultrasound of joints, enthesitis, skin and synovial tissue analysis, and “participation.”

PMID: 17477480 [PubMed - indexed for MEDLINE]

]]>

Related ArticlesOutcome measures in psoriatic arthritis.

J Rheumatol. 2007 May;34(5):1159-66

Authors: Gladman DD, Mease PJ, Healy P, Helliwell PS, Fitzgerald O, Cauli A, Lubrano E, Krueger GG, van der Heijde D, Veale DJ, Kavanaugh A, Nash P, Ritchlin C, Taylor W, Strand V

Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor, has emerged as a more common and severe disease than previously appreciated. The disease is multifaceted. Thus the assessment of PsA requires attention to peripheral joint involvement, axial disease, dactylitis, and enthesitis, as well as the skin manifestations. In addition, the assessment of patient reported features such as patient assessment of disease activity, pain, fatigue, quality of life, and the new concept of participation are important. The assessment of damage and the assessment of tissue histology are also important outcome measures. This article summarizes these features of PsA as well as current knowledge on the instruments available for the assessment of these domains.

PMID: 17477479 [PubMed - indexed for MEDLINE]

]]>

Related ArticlesAccuracy of the diagnoses of spondylarthritides in veterans affairs medical center databases.

Arthritis Rheum. 2007 May 15;57(4):648-55

Authors: Singh JA, Holmgren AR, Krug H, Noorbaloochi S

OBJECTIVE: To study the accuracy of diagnoses of spondylarthritides in computerized databases at the Minneapolis Veterans Affairs Medical Center. METHODS: Medical records were available and reviewed for a random sample of 184 patients from a cohort of 737 patients seen at the rheumatology clinic between January 1, 2001 and July 31, 2002. We compared 4 database definitions with the medical record gold standard of rheumatologists’ diagnosis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), or reactive arthritis (ReA): presence of 1) > or =1 or 2) > or =2 International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes for diagnoses of AS (720.0), PsA (696.0), and ReA (099.3, 711.11-711.19), and presence of 3) > or =1 or 4) > or =2 ICD-9 codes and prescription of a disease-modifying antirheumatic drug (DMARD). Accuracy was assessed by sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs), kappa statistic, and receiver operator characteristic (ROC) curve area. RESULTS: Of 184 patients, 11 (6%) had AS, 17 (9%) had PsA, and 7 (4%) had ReA as per the gold standard. ICD-9 codes for AS, PsA, and ReA were very specific (98-100%) with excellent NPV (99-100%) and PPV (83-100%), good to excellent sensitivity (57-100%), almost perfect kappa agreement (0.72-1), and high ROC curve area (0.79-1). Addition of presence of DMARD prescription to ICD-9 codes of AS and PsA decreased sensitivity to 27-65% without improving the specificity (which was already high at 99-100%). CONCLUSION: The ICD-9 codes for AS, PsA, and ReA in databases are accurate. ICD-9 codes may be used to identify cohorts of patients with spondylarthritides.

PMID: 17471541 [PubMed - indexed for MEDLINE]

]]>