{Reference Type}: Journal Article
{Author}: Yoshizaki, Ayumi; Yanaba, Koichi; Iwata, Yohei; Komura, Kazuhiro; Ogawa, Asako; Muroi, Eiji; Ogawa, Fumihide; Takenaka, Motoi; Shimizu, Kazuhiro; Hasegawa, Minoru; Fujimoto, Manabu; Sato, Shinichi
{Year}: 2011
{Title}: Elevated serum interleukin-27 levels in patients with systemic sclerosis: association with T cell, B cell and fibroblast activation
{Tag}: 0
{Star}: 0
{Journal}: ANNALS OF THE RHEUMATIC DISEASES
{Volume}: 70
{Issue}: 1
{Pages}: 194-200
{ISBN/ISSN}: 0003-4967
{Keywords}: CLINICAL CORRELATIONS; IMMUNE-RESPONSES; DENDRITIC CELLS; CUTTING EDGE; IL-27; RECEPTOR; CYTOKINE; DISEASE; SCLERODERMA; EXPRESSION
{Abstract}: Objective To determine serum levels of interleukin 27 (IL-27) in patients with systemic sclerosis (SSc) and relate the results to the clinical features of SSc.
Methods Serum levels of IL-27 in 91 patients with SSc and the production of IL-27 by isolated monocytes were examined by ELISA. The expression of IL-27 receptor in the skin fibroblasts, B cells and T cells was quantified by real-time PCR. The effect of IL-27 on immunoglobulin G (IgG) production of B cells, IL-17 production of CD4 T cells and proliferation and collagen synthesis of fibroblasts was also analysed.
Results Serum IL-27 levels were raised in patients with SSc compared with healthy controls and correlated positively with the extent of skin and pulmonary fibrosis and immunological abnormalities. IL-27 levels also correlated positively with serum levels of hyaluronan, recently identified as an endogenous ligand for Toll-like receptors. The retrospective longitudinal analysis showed a tendency for serum IL-27 levels to be attenuated during the follow-up period. IL-27 production by cultured monocytes was increased by hyaluronan stimulation. IL-27 receptor expression was upregulated in the affected skin fibroblasts, B cells and CD4 T cells of patients with SSc. Moreover, IL-27 stimulation increased IgG production of B cells, IL-17 production of CD4 T cells and proliferation and collagen synthesis of fibroblasts in patients with SSc compared with those in healthy controls.
Conclusion These results suggest that IL-27 and its signalling in B cells, T cells and fibroblasts contributes to disease development in patients with SSc.
{Author Address}: Nagasaki Univ, Dept Dermatol, Grad Sch Biomed Sci, Nagasaki 852, Japan; Nagasaki Univ, Dept Dermatol, Grad Sch Biomed Sci, Nagasaki 852, Japan; Nagasaki Univ, Dept Dermatol, Grad Sch Biomed Sci, Nagasaki 852, Japan; Kanazawa Univ, Dept Dermatol, Grad Sch Med Sci, Kanazawa, Ishikawa, Japan; Nagasaki Univ, Dept Dermatol, Grad Sch Biomed Sci, Nagasaki 852, Japan; Nagasaki Univ, Dept Dermatol, Grad Sch Biomed Sci, Nagasaki 852, Japan; Nagasaki Univ, Dept Dermatol, Grad Sch Biomed Sci, Nagasaki 852, Japan; Nagasaki Univ, Dept Dermatol, Grad Sch Biomed Sci, Nagasaki 852, Japan; Nagasaki Univ, Dept Dermatol, Grad Sch Biomed Sci, Nagasaki 852, Japan; Kanazawa Univ, Dept Dermatol, Grad Sch Med Sci, Kanazawa, Ishikawa, Japan; Kanazawa Univ, Dept Dermatol, Grad Sch Med Sci, Kanazawa, Ishikawa, Japan; Univ Tokyo, Dept Dermatol, Grad Sch Med, Bunkyo Ku, Tokyo 1138655, Japan; Nagasaki Univ, Dept Dermatol, Grad Sch Biomed Sci, Nagasaki 852, Japan
{Database Provider}: Web of Science SCI
{Language}: English
{Country}: Japan; Japan; Japan

{Reference Type}: Journal Article
{Author}: Tyndall, Anthony J.; Bannert, Bettina; Vonk, Madelon; Airo, Paolo; Cozzi, Franco; Carreira, Patricia E.; Bancel, Dominique Farge; Allanore, Yannick; Mueller-Ladner, Ulf; Distler, Oliver; Iannone, Florenzo; Pellerito, Raffaele; Pileckyte, Margarita; Miniati, Irene; Ananieva, Lidia; Gurman, Alexandra Balbir; Damjanov, Nemanja; Mueller, Adelheid; Valentini, Gabriele; Riemekasten, Gabriela; Tikly, Mohammed; Hummers, Laura; Henriques, Maria J. S.; Caramaschi, Paola; Scheja, Agneta; Rozman, Blaz; Ton, Evelien; Kumanovics, Gabor; Coleiro, Bernard; Feierl, Eva; Szucs, Gabriella; Von Muehlen, Carlos Alberto; Riccieri, Valeria; Novak, Srdan; Chizzolini, Carlo; Kotulska, Anna; Denton, Christopher; Coelho, Paulo C.; Koetter, Ina; Simsek, Ismail; de la Pena Lefebvre, Paloma Garcia; Hachulla, Eric; Seibold, James R.; Rednic, Simona; Stork, Jiri; Morovic-Vergles, Jadranka; Walker, Ulrich A.
{Year}: 2010
{Title}: Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database
{Tag}: 0
{Star}: 0
{Journal}: ANNALS OF THE RHEUMATIC DISEASES
{Volume}: 69
{Issue}: 10
{Pages}: 1809-1815
{ISBN/ISSN}: 0003-4967
{Keywords}: AUTOIMMUNE RHEUMATIC-DISEASES; INTERSTITIAL LUNG-DISEASE; POPULATION-BASED COHORT; PULMONARY-FIBROSIS; SURVIVAL; MORTALITY; ATHEROSCLEROSIS; MANIFESTATIONS; HYPERTENSION; ACCURACY
{Abstract}: Objectives To determine the causes and predictors of mortality in systemic sclerosis (SSc).
Methods Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality.
Results Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points).
Conclusion Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.
{Author Address}: Univ Basel, Dept Rheumatol, CH-4012 Basel, Switzerland; Univ Basel, Dept Rheumatol, CH-4012 Basel, Switzerland; Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands; Serv Reumatol Allergol & Immunol Clin, Brescia, Italy; Univ Padua, Rheumatol Unit, Dept Clin & Expt Med, Padua, Italy; Hosp Univ 12 Octubre, Serv Reumatol, Madrid, Spain; Hop St Louis, Dept Internal Med, Paris, France; Hop Cochin, Dept Rheumatol, F-75674 Paris, France; Max Planck Inst Physiol & Clin Res, Kerckhoff Klin, Abt Rheumatol, D-6350 Bad Nauheim, Germany; Max Planck Inst Physiol & Clin Res, Kerckhoff Klin, Klin Immunol, D-6350 Bad Nauheim, Germany; Univ Zurich Hosp, Dept Rheumatol, CH-8091 Zurich, Switzerland; Univ Bari, UO Reumatol, Bari, Italy; Osped Mauriziano Umberto 1, Ctr Reumatol, Turin, Italy; Kaunas Univ, Hosp Med, Dept Rheumatol, Kaunas, Lithuania; Univ Florence, Div Rheumatol AOUC, Dept Biomed, Florence, Italy; Russian Acad Med Sci, Inst Rheumatol, Moscow 109801, Russia; Rambam Hlth Care Campus, Shine Dept Rheumatol B, Haifa, Israel; Inst Rheumatol, Belgrade, Serbia; Univ Regensburg, Dept Internal Med 1, Regensburg, Germany; Policlin UO Reumatol, Dipartimento Med Clin & Sperimentale F Magrassi 2, Naples, Italy; Charite, Dept Rheumatol, Berlin, Germany; Hosp & Univ Witwatersrand, Johannesburg, South Africa; Dept Med Chris Hani Baragwanath, Rheumatol Unit, Johannesburg, South Africa; Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA; Hosp Univ Coimbra, Coimbra, Portugal; Univ Verona, Dipartimento Med Clin & Sperimentale, I-37100 Verona, Italy; Univ Lund Hosp, Dept Rheumatol, S-22185 Lund, Sweden; Univ Med Ctr, Dept Rheumatol, Ljubljana, Slovenia; Univ Med Ctr, Utrecht, Netherlands; Univ Pecs, Dept Immunol & Rheumatol, Pecs, Hungary; Stella Maris Balzan, Balzan, Malta; Med Univ Vienna, Div Rheumatol, Vienna, Austria; Debrecen Univ Med, Dept Rheumatol, Inst Internal Med, H-4012 Debrecen, Hungary; Hlth Sci Ctr, Debrecen, Hungary; Rheuma Clin, Porto Alegre, RS, Brazil; Univ Roma La Sapienza, Div Reumatol, Rome, Italy; KBC Rijeka, Dept Rheumatol & Clin Immunol, Rijeka, Croatia; Univ Hosp, Dept Immunol & Allergy, Geneva, Switzerland; Med Univ Silesia, Dept Internal Med & Rheumatol, Katowice, Poland; Royal Free & Univ Coll Med Sch, Ctr Rheumatol, London, England; Inst Portugues Reumatol, Lisbon, Portugal; Univ Klinikum Tubingen, Tubingen, Germany; Gulhane Mil Med Acad, Div Rheumatol, Ankara, Turkey; Hosp Ramon & Cajal, Serv Reumatol, E-28034 Madrid, Spain; Hop Claude Huriez, Dept Internal Med, Lille, France; Univ Michigan, Scleroderma Program, Ann Arbor, MI 48109 USA; Univ Med & Pharm Iuliu Hatieganu, Clin Reumatol, Cluj Napoca, Romania; Charles Univ Prague, Dept Dermatol, Prague, Czech Republic; Dubrava Univ Hosp, Div Clin Immunol & Rheumatol, Zagreb, Croatia; Univ Basel, Dept Rheumatol, CH-4012 Basel, Switzerland
{Database Provider}: Web of Science SCI
{Language}: English
{Country}: Switzerland; Netherlands; Italy; Italy; Spain; France; France; Germany; Germany; Switzerland; Italy; Italy; Lithuania; Italy; Russia; Israel; Serbia; Germany; Italy; Germany; South Africa; South Africa; USA; Portugal; Italy; Sweden; Slovenia; Netherlands; Hungary; Malta; Austria; Hungary; Hungary; Brazil; Italy; Croatia; Switzerland; Poland; England; Portugal; Germany; Turkey; Spain; France; USA; Romania; Czech Republic; Croatia

{Reference Type}: Journal Article
{Author}: Eloranta, Maija-Leena; Franck-Larsson, Karin; Lovgren, Tanja; Kalamajski, Sebastian; Ronnblom, Anders; Rubin, Kristofer; Alm, Gunnar V.; Ronnblom, Lars
{Year}: 2010
{Title}: Type I interferon system activation and association with disease manifestations in systemic sclerosis
{Tag}: 0
{Star}: 0
{Journal}: ANNALS OF THE RHEUMATIC DISEASES
{Volume}: 69
{Issue}: 7
{Pages}: 1396-1402
{ISBN/ISSN}: 0003-4967
{Keywords}: PRIMARY SJOGRENS-SYNDROME; PLASMACYTOID DENDRITIC CELLS; PERIPHERAL-BLOOD CELLS; LUPUS-ERYTHEMATOSUS; GENE-EXPRESSION; IMMUNE-COMPLEXES; ALPHA; SCLERODERMA; RNA; AUTOANTIBODIES
{Abstract}: Objectives To study the presence of interferogenic autoantibodies in systemic sclerosis (SSc) and their correlation with clinical manifestations, serum levels of interferon alpha (IFN alpha) and chemokines of importance in the disease process.
Methods Peripheral blood mononuclear cells (PBMCs) or purified plasmacytoid dendritic cells (pDCs) from healthy donors were stimulated with sera from patients with SSc (n=70) or healthy individuals (n=30), together with necrotic or apoptotic cell material. The IFN alpha produced and serum levels of IFN alpha, IFN-inducible protein-10 (IP-10)/chemokine (C-X-C motif) ligand 10, monocyte chemoattractant protein-1 (MCP-1)/(C-C motif) ligand-2 (CCL-2), macrophage inflammatory protein-1 alpha (MIP-1 alpha)/CCL-3 and RANTES/CCL-5 were measured and correlated with the presence of autoantibodies and clinical manifestations in the patients with SSc.
Results Sera from both diffuse SSc and limited SSc contained interferogenic antibodies, which correlated with the presence of anti-ribonucleoprotein and anti-Sjogren syndrome antigen autoantibodies. The pDCs were responsible for the IFN alpha production which required interaction with Fc gamma RII and endocytosis. Increased serum levels of IP-10 were associated with vascular manifestations such as cardiac involvement (p=0.027) and pulmonary arterial hypertension (p=0.036). Increased MCP-1 or IFN alpha serum levels were associated with lung fibrosis (p=0.019 and 0.048, respectively). Digital ulcers including digital loss were associated with increased serum levels of IFN alpha (p=0.029).
Conclusion An activated type I IFN system previously seen in several other systemic autoimmune diseases is also present in SSc and may contribute to the vascular pathology and affect the profibrotic process.
{Author Address}: Uppsala Univ, Dept Med Sci, Uppsala, Sweden; Uppsala Univ, Dept Med Sci, Uppsala, Sweden; Wyeth AB, Solna, Sweden; Uppsala Univ, Dept Med Sci, Uppsala, Sweden; Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden; Uppsala Univ, Dept Med Sci, Uppsala, Sweden; Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden; Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden; Uppsala Univ, Dept Med Sci, Uppsala, Sweden
{Database Provider}: Web of Science SCI
{Language}: English
{Country}: Sweden; Sweden; Sweden; Sweden

{Reference Type}: Journal Article
{Author}: Huegle, 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?
{Tag}: 0
{Star}: 0
{Journal}: ANNALS OF THE RHEUMATIC DISEASES
{Volume}: 68
{Issue}: 1
{Pages}: 47-50
{ISBN/ISSN}: 0003-4967
{Keywords}: SYSTEMIC-LUPUS-ERYTHEMATOSUS; ALPHA THERAPY; HEPATITIS-C; SCLERODERMA; COEXISTENCE; PATIENT; DISEASE
{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}: Univ Basel, Dept Rheumatol, Felix Platter Spital, CH-4003 Basel, Switzerland; Univ Basel, Dept Rheumatol, Felix Platter Spital, CH-4003 Basel, Switzerland; Univ Basel, Dept Rheumatol, Felix Platter Spital, CH-4003 Basel, Switzerland; Univ Basel, Dept Rheumatol, Felix Platter Spital, CH-4003 Basel, Switzerland; Univ Basel, Dept Rheumatol, Felix Platter Spital, CH-4003 Basel, Switzerland; Univ Basel, Dept Rheumatol, Felix Platter Spital, CH-4003 Basel, Switzerland
{Database Provider}: Web of Science SCI
{Language}: English
{Country}: Switzerland