{Reference Type}: Journal Article
{Author}: Yoon, K. H.
{Year}: 2009
{Title}: Proliferation signal inhibitors for the treatment of refractory autoimmune rheumatic diseases: a new therapeutic option
{URL}: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19758225&query_hl=1
{Tag}: 0
{Star}: 0
{Journal}: Ann N Y Acad Sci
{Volume}: 1173
{Pages}: 752-6
{DOI}: 10.1111/j.1749-6632.2009.04663.x
{Date Displayed}: 2009 Sep
{Date}: 2009-09-01
{Type of Work}: Journal Article
{Accession Number}: 19758225
{Keywords}: Adult; Aged; Arthritis, Psoriatic/drug therapy; Arthritis, Rheumatoid/drug therapy; Autoimmune Diseases/*drug therapy; Drug Resistance; Female; Humans; Immunosuppressive Agents/chemistry/therapeutic use; Lupus Erythematosus, Systemic/drug therapy; Male; Middle Aged; Molecular Structure; Retrospective Studies; Rheumatic Diseases/*drug therapy; Scleroderma, Systemic/drug therapy; Sirolimus/*analogs & derivatives/chemistry/*therapeutic use; Spondylarthropathies/drug therapy; Treatment Outcome; Vasculitis/drug therapy
{Abstract}: Sirolimus and everolimus belong to the novel class of immunosuppressant agents known as proliferation signal inhibitors (PSIs). They act by preventing antigen-driven T cell proliferation. While PSIs are widely used in transplantation, there are few reports of PSI usage in the treatment of autoimmune rheumatic diseases. The author has presented a series in the APLAR 2006 conference. This report summarizes the clinical experience with PSIs in the   treatment of resistant or relapsed rheumatic diseases where conventional immunosuppressive agents have failed. This is a retrospective review of patients   with various autoimmune rheumatic diseases who had sirolimus and everolimus treatment from the rheumatological clinics of Changi Hospital or the Arthritis and Rheumatism Specialist Medical Centre. The period of review was from April 2006 to April 2008. A total of 46 patients were reviewed, 39 females and 7 males. The racial distribution was 33 Chinese, 7 Malays, and 6 Indians. Their disease conditions were as follows: 26 (57%) rheumatoid arthritis, 7 psoriatic arthritis, 4 systemic lupus erythematosus, 3 scleroderma, 2 anti-Jo-1 syndrome, 2 spondyloarthropathy, 1 MCTD, and 1 vasculitis. All patients had failed at least three DMARDs or immunosuppressants. Twenty-eight patients received sirolimus and   28 patients received everolimus. Overall positive response rate was 48.2%. Twenty-seven percent had adverse events. 20% had no response. 7% relapsed after initial response. PSIs, namely sirolimus and everolimus, are a novel class of immunosuppressants that can be added to the armamentarium of rheumatologists for   the treatment of patients with refractory autoimmune rheumatic diseases.
{Author Address}: Arthritis & Rheumatism Specialist Medical Centre, and Department of Medicine, Changi General Hospital, Singapore. mdcykh@singnet.com.sg
{Language}: eng

{Reference Type}: Journal Article
{Author}: Waterhouse, J. C.; Perez, T. H.; Albert, P. J.
{Year}: 2009
{Title}: Reversing bacteria-induced vitamin D receptor dysfunction is key to autoimmune disease
{URL}: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19758226&query_hl=1
{Tag}: 0
{Star}: 0
{Journal}: Ann N Y Acad Sci
{Volume}: 1173
{Pages}: 757-65
{DOI}: 10.1111/j.1749-6632.2009.04637.x
{Date Displayed}: 2009 Sep
{Date}: 2009-09-01
{Type of Work}: Journal Article
{Accession Number}: 19758226
{Keywords}: Animals; Anti-Bacterial Agents/therapeutic use; Arthritis, Reactive/drug therapy/metabolism/physiopathology; Arthritis, Rheumatoid/drug therapy/metabolism/physiopathology; Autoimmune Diseases/drug therapy/metabolism/*physiopathology; Bacterial Infections/drug therapy/*physiopathology; Calcifediol/metabolism; Calcitriol/metabolism; Diabetes Mellitus, Type 1/drug therapy/metabolism/physiopathology; Diabetes Mellitus, Type 2/drug therapy/metabolism/physiopathology; Humans; Imidazoles/therapeutic use; Minocycline/therapeutic use; Psoriasis/drug therapy/metabolism/physiopathology; Receptors, Calcitriol/agonists/*physiology; Sarcoidosis/drug therapy/metabolism/physiopathology; Scleroderma, Systemic/drug therapy/metabolism/physiopathology; Sjogren's Syndrome/drug therapy/metabolism/physiopathology; Spondylitis, Ankylosing/drug therapy/metabolism/physiopathology; Tetrazoles/therapeutic use; Thyroid Diseases/drug therapy/metabolism/physiopathology; Uveitis/drug therapy/metabolism/physiopathology
{Abstract}: Vitamin D research is discussed in light of the hypothesis that the lower average levels of vitamin D frequently observed in autoimmune disease are not a sign of deficiency. Instead, it is proposed that the lower levels result from chronic infection with intracellular bacteria that dysregulate vitamin D metabolism by causing vitamin D receptor (VDR) dysfunction within phagocytes. The VDR dysfunction causes a decline in innate immune function that causes susceptibility to additional infections that contribute to disease progression. Evidence has been accumulating that indicates that a number of autoimmune diseases can be reversed by gradually restoring VDR function with the VDR agonist olmesartan and   subinhibitory dosages of certain bacteriostatic antibiotics. Diseases showing favorable responses to treatment so far include systemic lupus erythematosis, rheumatoid arthritis, scleroderma, sarcoidosis, Sjogren's syndrome, autoimmune thyroid disease, psoriasis, ankylosing spondylitis, Reiter's syndrome, type I and II diabetes mellitus, and uveitis. Disease reversal using this approach requires   limitation of vitamin D in order to avoid contributing to dysfunction of nuclear   receptors and subsequent negative consequences for immune and endocrine function. Immunopathological reactions accompanying bacterial cell death require a gradual   elimination of pathogens over several years. Practical and theoretical implications are discussed, along with the compatibility of this model with current research.
{Author Address}: Autoimmunity Research Foundation, Thousand Oaks, California 91360, USA. jcw@autoimmunityresearch.org
{Language}: eng

{Reference Type}: Journal Article
{Author}: Klein, S.; Kretz, C. C.; Ruland, V.; Stumpf, C.; Haust, M.; Hartschuh, W.; Hartmann, M.; Enk, A.; Suri-Payer, E.; Oberle, N.; Krammer, P. H.; Kuhn, A.
{Year}: 2011
{Title}: Reduction of regulatory T cells in skin lesions but not in peripheral blood of patients with systemic scleroderma
{URL}: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21097800&query_hl=1
{Tag}: 0
{Star}: 0
{Journal}: Ann Rheum Dis
{Volume}: 70
{Issue}: 8
{Pages}: 1475-81
{DOI}: 10.1136/ard.2009.116525
{Date Displayed}: 2011 Aug
{Date}: 2011-08-01
{Type of Work}: Journal Article; Research Support, Non-U.S. Gov't
{Accession Number}: 21097800
{Keywords}: Adult; Aged; Biopsy; CD4-Positive T-Lymphocytes/immunology; Case-Control Studies; Dermatitis/immunology; Dermatologic Agents/pharmacology/therapeutic use; Female; Forkhead Transcription Factors/analysis; Humans; Immune Tolerance/immunology; Male; Middle Aged; Receptor, Endothelin A/antagonists & inhibitors; Scleroderma, Localized/immunology; Scleroderma, Systemic/drug therapy/*immunology/pathology; Skin/*immunology/pathology; Sulfonamides/pharmacology/therapeutic use; T-Lymphocyte Subsets/immunology; T-Lymphocytes, Regulatory/drug effects/*immunology
{Abstract}: OBJECTIVE: To determine the frequency and suppressive capacity of regulatory T cells (T(reg)) and their association with clinical parameters in patients with systemic scleroderma (SSc). METHODS: Peripheral blood from 25 patients with SSc,   15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was studied. Analysis of CD4(+) forkhead box P3 (Foxp3)(+) and CD4(+)CD25(++)Foxp3(+) T(reg) subpopulations was carried out by flow cytometry and cell proliferation was quantified by (3)H-thymidine incorporation. Quantitative analysis of T(reg) was further performed in skin biopsies from 17 patients with SSc and 21 patients   with LS using anti-CD4 and anti-Foxp3 monoclonal antibodies for immunohistochemistry. RESULTS: The frequency of CD4(+)Foxp3(+) and CD4(+)CD25(++)Foxp3(+) T(reg) in peripheral blood from patients with SSc was not   significantly different from that of patients with LS or HC. The suppressive capacity of CD4(+)CD25(++) T(reg) in SSc was also found to be similar to that of   HC. Phenotypic and functional data revealed no significant difference between the limited or diffuse form of SSc. Moreover, therapy with bosentan showed no significant effect on the frequency of T(reg) during the course of the disease. However, the frequency of T(reg) in skin lesions from patients with SSc or LS, determined as the percentage of CD4(+) cells expressing Foxp3 in the inflammatory infiltrate, was significantly reduced compared with other inflammatory skin diseases. CONCLUSION: These results indicate that although the authors found no defect in the frequency or function of peripheral T(reg) subpopulations, the reduction of CD4(+)Foxp3(+) T(reg) in the skin of patients with SSc may be important in the pathogenesis of the disease.
{Author Address}: Division of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany.
{Language}: eng

{Reference Type}: Journal Article
{Author}: Hugle, T.; Gratzl, S.; Daikeler, T.; Frey, D.; Tyndall, A.; Walker, U. A.
{Year}: 2009
{Title}: Sclerosing skin disorders in association with multiple sclerosis. Coincidence, underlying autoimmune pathology or interferon induced?
{URL}: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18203763&query_hl=1
{Tag}: 0
{Star}: 0
{Journal}: Ann Rheum Dis
{Volume}: 68
{Issue}: 1
{Pages}: 47-50
{DOI}: 10.1136/ard.2007.083246
{Date Displayed}: 2009 Jan
{Date}: 2009-01-01
{Type of Work}: Case Reports; Journal Article; Review
{Accession Number}: 18203763
{Keywords}: Adjuvants, Immunologic/adverse effects/therapeutic use; Aged; Female; Humans; Interferon-beta/adverse effects/therapeutic use; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting/*complications/immunology; Raynaud Disease/complications/immunology; Scleroderma, Diffuse/*complications/immunology; Time Factors
{Abstract}: OBJECTIVES: To describe and analyse the manifestation of sclerosing skin disorders in patients with multiple sclerosis (MS). CASE REPORTS: We describe three patients with relapsing-remitting MS who developed skin sclerosis while receiving interferon (IFN)-beta treatment and review nine further cases of systemic sclerosis (SSc) in MS from the literature. Of all 12 patients reported,   eight had limited cutaneous SSc, three had diffuse cutaneous SSc and one patient   had an antisynthetase syndrome. Localised scleroderma such as morphoea was not described. The mean age at diagnosis was 25.2 years for MS (range 12 to 51) and 38.3 years for SSc (range 16 to 66). Eleven patients developed SSc after the onset of MS and manifested with skin sclerosis after a mean of 14.9 years (range   1 to 45). In five patients IFN-beta was commenced before the development of skin   sclerosis (mean 4.6 years, range 1 to 8 years). There was no relationship between the onset of skin sclerosis and MS activity. With the exception of one individual, all patients had antinuclear antibodies. CONCLUSIONS: Sclerosing skin disorders may develop in the course of MS. The relatively early age of SSc onset   in patients with MS suggests a genetic predisposition and/or an IFN-associated trigger.
{Author Address}: Felix Platter Spital, Basel University Department of Rheumatology, Switzerland.
{Language}: eng