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Marvin J. Fritzler - One of the best experts on this subject based on the ideXlab platform.
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Anti-Centromere Antibodies in a large cohort of systemic sclerosis patients: comparison between immunofluorescence, CENP-A and CENP-B ELISA.
Clinica Chimica Acta, 2011Co-Authors: Michael Mahler, Daniel You, Murray Baron, Suzanne Taillefer, Marie Hudson, Marvin J. FritzlerAbstract:Abstract Introduction Anti-Centromere Antibodies (ACA) are useful biomarkers in the diagnosis of systemic sclerosis (SSc) where they are found in 20–40% of patients and, albeit with lower prevalence, in patients with other systemic autoimmune rheumatic diseases. Historically, ACA were detected by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed by immunoassays using recombinant CENP-B. During the last few years, to accommodate high throughput diagnostics, a number of laboratories changed from IIF to ELISA assays. The objective of this study was to compare the detection of ACA by IIF to CENP-A and a CENP-B ELISA in a large cohort of SSc patients. Methods Sera collected from SSc patients (n = 834) were tested for ACA by IIF on HEp-2 cells (ImmunoConcepts, Sacramento, CA) and CENP-A and CENP-B ELISA (both Dr. Fooke Laboratorien GmbH, Neuss, Germany). Furthermore, other autoAntibodies were determined by QUANTA-PlexTM SLE 8 profile (INOVA, San Diego, CA), QUANTA Lite® RNA Pol III (INOVA) and PM1-Alpha ELISA (Dr. Fooke). Results The prevalence of ACA was 35.0% by IIF, 41.6% by CENP-A and 57.8% by CENP-B ELISA. When the CENP-A and the CENP-B ELISA results were compared to the IIF, the area under the curve value derived from receiver operating characteristic analysis was 0.98 for both assays. ACA and anti-topoisomerase I Antibodies co-occurred in 1.2% (ACA by IIF), in 3.5% (by CENP-A ELISA) and in 7.4% (by CENP-B ELISA). Anti-CENP-A Antibodies were negatively associated with anti-Scl-70, anti-RNA Pol III, (both p Conclusion Although we found good agreement between IIF and ELISA for the detection of ACA in SSc, a significant portion of CENP ELISA positive sera did not show the typical ACA staining pattern. Based on these findings, we conclude that an IIF ACA negative result might not rule out the presence of ACA. In addition, new CENP ELISA kits are reliable for the detection of anti-CENP in SSc sera.
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Anti-Centromere Antibodies in a large cohort of systemic sclerosis patients: comparison between immunofluorescence, CENP-A and CENP-B ELISA.
Clinica chimica acta; international journal of clinical chemistry, 2011Co-Authors: Michael Mahler, Daniel You, Murray Baron, Suzanne Taillefer, Marie Hudson, Marvin J. FritzlerAbstract:Anti-Centromere Antibodies (ACA) are useful biomarkers in the diagnosis of systemic sclerosis (SSc) where they are found in 20-40% of patients and, albeit with lower prevalence, in patients with other systemic autoimmune rheumatic diseases. Historically, ACA were detected by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed by immunoassays using recombinant CENP-B. During the last few years, to accommodate high throughput diagnostics, a number of laboratories changed from IIF to ELISA assays. The objective of this study was to compare the detection of ACA by IIF to CENP-A and a CENP-B ELISA in a large cohort of SSc patients. Sera collected from SSc patients (n=834) were tested for ACA by IIF on HEp-2 cells (ImmunoConcepts, Sacramento, CA) and CENP-A and CENP-B ELISA (both Dr. Fooke Laboratorien GmbH, Neuss, Germany). Furthermore, other autoAntibodies were determined by QUANTA-Plex(TM) SLE 8 profile (INOVA, San Diego, CA), QUANTA Lite RNA Pol III (INOVA) and PM1-Alpha ELISA (Dr. Fooke). The prevalence of ACA was 35.0% by IIF, 41.6% by CENP-A and 57.8% by CENP-B ELISA. When the CENP-A and the CENP-B ELISA results were compared to the IIF, the area under the curve value derived from receiver operating characteristic analysis was 0.98 for both assays. ACA and anti-topoisomerase I Antibodies co-occurred in 1.2% (ACA by IIF), in 3.5% (by CENP-A ELISA) and in 7.4% (by CENP-B ELISA). Anti-CENP-A Antibodies were negatively associated with anti-Scl-70, anti-RNA Pol III, (both p<0.0001), anti-U1-RNP (p=0.008) and anti-PM1-Alpha Antibodies (p=0.0337). The degree of association was dependent on the cut-off value used. Although we found good agreement between IIF and ELISA for the detection of ACA in SSc, a significant portion of CENP ELISA positive sera did not show the typical ACA staining pattern. Based on these findings, we conclude that an IIF ACA negative result might not rule out the presence of ACA. In addition, new CENP ELISA kits are reliable for the detection of anti-CENP in SSc sera. Copyright © 2011 Elsevier B.V. All rights reserved.
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Primary biliary cirrhosis and autoAntibodies.
Japanese Journal of Clinical Immunology, 2008Co-Authors: K. Miyachi, Hiroshi Miyakawa, Oda M, Tsuneyoshi Horigome, Marvin J. FritzlerAbstract:Abstract Fifty years have passed since anti-mitochondrial Antibodies were found in patients with primary biliary cirrhosis (PBC). PBC is an autoimmune hepatic disease in which 85-90% of patient Antibodies bind to mitochondrial antigens that include pyruvate dehydrogenase complex (PDC)-E2 and other members of the oxaloacid dehydrogenase family. In addition, indirect immunofluorescence (IIF) assays utilizing HEp-2 cell substrates have been used to identify Anti-Centromere Antibodies in 20-30% of PBC sera. These Antibodies are generally easily recognized, however, anti-nuclear envelope and anti-multiple nuclear dot Antibodies are occasionally more difficult to recognize with certainty by IIF. The use of enzyme linked immunosorbent assays that utilize recombinant gp210 (an autoantigen of the nuclear envelope) and/or sp100 (a protein target represented by multiple nuclear dots) should be particularly considered in anti-mitochondrial antibody negative PBC sera. Although the clinical significance of these Antibodies still remains to be determined, there is evidence that the existence of anti-gp210 Antibodies are related to poorer prognosis and more aggressive disease progression.
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A case of limited cutaneous systemic sclerosis developing anti-mitochondria antibody positive primary biliary cirrhosis after acute myocardial infarction.
Clinical Rheumatology, 2006Co-Authors: Kiyomitsu Miyachi, Tetsuroh Okano, Raleigh W. Hankins, Minoru Ihara, Akira Miyamoto, Miwako Iwai, Katsuhiko Mikoshiba, Marvin J. FritzlerAbstract:In this report, we present a 63-year-old woman who had limited cutaneous systemic sclerosis and subsequently developed typical primary biliary cirrhosis after an acute myocardial infarction. The patient initially developed Raynaud's phenomenon, and 4 years later visited the clinic in 1994 complaining of abdominal distress, xerostomia, and xerophthalmia. A diagnosis of limited cutaneous systemic sclerosis was based on Raynaud's phenomenon, sclerodactyly and Anti-Centromere Antibodies. She was also found to have anti-inositol 1,4,5-trisphosphate receptor 3 (IP(3)R3) Antibodies, but anti-mitochondrial Antibodies were only weakly positive. Seven years later, she developed vertigo and nausea, and was hospitalized due to complaints of an oppressive sensation of the anterior chest. Electrocardiogram results showed a reduction of R waves and ST segment elevation in II, III, and aVf leads. Coronary angiography showed 99% obstruction of the left anterior descending artery and 50% of stenosis of the right coronary artery. Three years later, the patient was noted to have anti-mitochondrial Antibodies. Retrospective analysis of the patient's sera showed that IP(3)R3 Antibodies were decreasing. Since myocardium is particularly rich in mitochondria, it is thought that myocardial infarction may have been the triggering event that initiated antigen-presenting cells to selectively induce an anti-mitochondrial antibody response.
Kiyoshi Migita - One of the best experts on this subject based on the ideXlab platform.
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Genetic polymorphisms in CTLA4 and SLC4A2 are differentially associated with the pathogenesis of primary biliary cirrhosis in Japanese patients
Journal of gastroenterology, 2011Co-Authors: Yoshihiro Aiba, Kiyoshi Migita, Minoru Nakamura, Atsumasa Komori, Hitomi Horie, Satoru Joshita, Tatsuo Inamine, Kaname Yoshizawa, Takeji Umemura, Hiroshi YatsuhashiAbstract:Background Anti-gp210 and Anti-Centromere Antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). In order to dissect the genetic basis for the production of these autoAntibodies, as well as the development and progression of PBC in Japanese patients, we examined single nucleotide polymorphisms (SNPs) in cytotoxic T-lymphocyte antigen 4 (CTLA4) and solute carrier family 4 anion exchanger, member 2 (SLC4A2), which have been associated with the pathogenesis of PBC in Caucasian patients.
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Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA-DRB1polymorphism determines the relative risk of antinuclear Antibodies for disease progression in PBC
Hepatology research : the official journal of the Japan Society of Hepatology, 2010Co-Authors: Minoru Nakamura, Kiyoshi Migita, Hisayoshi Kondo, Atsumasa Komori, Masahiro Ito, Michio Yasunami, Hitomi Horie, Yoshihiro Aiba, Hiroshi Yatsuhashi, Shinji ShimodaAbstract:Aims: Anti-gp210 and Anti-Centromere Antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA-DRB1 genotype in 334 Japanese PBC patients and studied their serum Antibodies to gp210 and centromere during the 1–452-month observation period. Results: Anti-gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20–850.1) and Anti-Centromere Antibodies (OR, 2.36, 95% CI, 1.28–4.35) were significant risk factors for jaundice- and nonjaundice-type progression, respectively. HLA-DRB1*0405 and *0803 predisposed patients to anti-gp210 (OR, 1.61, 95% CI, 1.08–2.39) and Anti-Centromere (OR, 2.30, 95% CI, 1.41–3.73) antibody production, respectively. HLA-DRB1*1502 and *0901 patients were predisposed to nonjaundice-type progression (OR, 1.98, 95% CI, 1.13–3.40 and OR, 1.78, 95% CI, 1.02–3.03), while HLA-DRB1*0803 and *0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48–3.41 and OR, 1.53, 95% CI, 1.11–2.11, respectively). Stratifying patients by HLA-DRB1 alleles revealed that anti-gp210 Antibodies was a strong risk factor, regardless of the HLA-DRB1 alleles for jaundice-type progression, while Anti-Centromere Antibodies was a significant risk factor for nonjaundice-type progression in patients with HLA-DRB1*0405 (OR, 6.89, 95% CI, 2.18–26.56) and -DRB1*0803 (OR, 5.42, 95% CI, 1.47–24.62) but not other HLA-DRB1 alleles. Conclusions: HLA-DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear Antibodies that contribute to PBC disease progression.
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anti gp210 and anti centromere Antibodies are different risk factors for the progression of primary biliary cirrhosis
Hepatology, 2007Co-Authors: Minoru Nakamura, Hisayoshi Kondo, Tsuyoshi Mori, Atsumasa Komori, Mutsumi Matsuyama, Masahiro Ito, Yasushi Takii, Makiko Koyabu, Terufumi Yokoyama, Kiyoshi MigitaAbstract:The predictive role of antinuclear Antibodies (ANAs) remains elusive in the long-term outcome of primary biliary cirrhosis (PBC). The progression of PBC was evaluated in association with ANAs using stepwise Cox proportional hazard regression and an unconditional stepwise logistic regression model based on the data of 276 biopsy-proven, definite PBC patients who have been registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). When death of hepatic failure/liver transplantation (LT) was defined as an end-point, positive anti-gp210 Antibodies (Hazard ratio (HR) = 6.742, 95% confidence interval (CI): 2.408, 18.877), the late stage (Scheuer's stage 3, 4) (HR = 4.285, 95% CI:1.682,10.913) and male sex (HR = 3.266, 95% CI: 1.321,8.075) were significant risk factors at the time of initial liver biopsy. When clinical progression to death of hepatic failure/LT (i.e., hepatic failure type progression) or to the development of esophageal varices or hepatocellular carcinoma without developing jaundice (Total bilirubin < 1.5 mg/dL) (i.e., portal hypertension type progression) was defined as an end-point in the early stage (Scheuer's stage 1, 2) PBC patients, positive anti-gp210 Antibodies was a significant risk factor for hepatic failure type progression [odds ratio (OR) = 33.777, 95% CI: 5.930, 636.745], whereas positive Anti-Centromere Antibodies was a significant risk factor for portal hypertension type progression (OR = 4.202, 95% CI: 1.307, 14.763). Histologically, positive anti-gp210 Antibodies was most significantly associated with more severe interface hepatitis and lobular inflammation, whereas positive anticentromere Antibodies was most significantly associated with more severe ductular reaction. Conclusion: These results indicate 2 different progression types in PBC, hepatic failure type and portal hypertension type progression, which may be represented by positive-anti-gp210 and positive-anticentromere Antibodies, respectively. (HEPATOLOGY 2007;45:118–127.)
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Anti‐gp210 and anti‐centromere Antibodies are different risk factors for the progression of primary biliary cirrhosis
Hepatology (Baltimore Md.), 2006Co-Authors: Minoru Nakamura, Hisayoshi Kondo, Tsuyoshi Mori, Atsumasa Komori, Mutsumi Matsuyama, Masahiro Ito, Yasushi Takii, Makiko Koyabu, Terufumi Yokoyama, Kiyoshi MigitaAbstract:The predictive role of antinuclear Antibodies (ANAs) remains elusive in the long-term outcome of primary biliary cirrhosis (PBC). The progression of PBC was evaluated in association with ANAs using stepwise Cox proportional hazard regression and an unconditional stepwise logistic regression model based on the data of 276 biopsy-proven, definite PBC patients who have been registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). When death of hepatic failure/liver transplantation (LT) was defined as an end-point, positive anti-gp210 Antibodies (Hazard ratio (HR) = 6.742, 95% confidence interval (CI): 2.408, 18.877), the late stage (Scheuer's stage 3, 4) (HR = 4.285, 95% CI:1.682,10.913) and male sex (HR = 3.266, 95% CI: 1.321,8.075) were significant risk factors at the time of initial liver biopsy. When clinical progression to death of hepatic failure/LT (i.e., hepatic failure type progression) or to the development of esophageal varices or hepatocellular carcinoma without developing jaundice (Total bilirubin < 1.5 mg/dL) (i.e., portal hypertension type progression) was defined as an end-point in the early stage (Scheuer's stage 1, 2) PBC patients, positive anti-gp210 Antibodies was a significant risk factor for hepatic failure type progression [odds ratio (OR) = 33.777, 95% CI: 5.930, 636.745], whereas positive Anti-Centromere Antibodies was a significant risk factor for portal hypertension type progression (OR = 4.202, 95% CI: 1.307, 14.763). Histologically, positive anti-gp210 Antibodies was most significantly associated with more severe interface hepatitis and lobular inflammation, whereas positive anticentromere Antibodies was most significantly associated with more severe ductular reaction. Conclusion: These results indicate 2 different progression types in PBC, hepatic failure type and portal hypertension type progression, which may be represented by positive-anti-gp210 and positive-anticentromere Antibodies, respectively. (HEPATOLOGY 2007;45:118–127.)
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HTLV-I associated Sjögren’s syndrome is aetiologically distinct from Anti-Centromere Antibodies positive Sjögren’s syndrome
Annals of the rheumatic diseases, 1999Co-Authors: Ayumi Hida, Yojiro Kawabe, Atsushi Kawakami, Kiyoshi Migita, Masahiro Tominaga, Hideki Nakamura, Katsumi EguchiAbstract:OBJECTIVE To investigate whether Sjogren’s syndrome (SS) with anti-HTLV-I Antibodies is aetiopathologically distinguishable from SS without these Antibodies, the study compared prevalence of autoAntibodies in serum samples of SS patients with or without anti-HTLV-I Antibodies. METHODS The test group included 135 patients with primary SS and 97 patients with secondary SS. Serum samples of the patients were examined for the presence of anti-nuclear Antibodies (ANA), anti-SS-A/Ro Antibodies, anti-SS-B/La Antibodies, Anti-Centromere Antibodies (ACA), and anti-HTLV-I Antibodies. RESULTS Anti-HTLV-I Antibodies were detected in 25.0% of primary SS patients and in 29.2% of secondary SS patients. There were no significant differences in the mean age, sex, values of asparate aminotransferase, alanine aminotransferase, alkaline phosphatase, serum complements and IgG between HTLV-I seropositive and seronegative SS patients. The rheumatoid factor, ANA, anti-SS-A/Ro, and anti-SS-B/La Antibodies in serum samples of SS patients were detected in 60.0%, 84.0%, 51.9%, and 12.0%, respectively. There was no significant difference in the prevalence of these Antibodies between HTLV-I seropositive and seronegative SS patients. Using the indirect immunofluorescence test, 14.2% showed a discrete speckled staining pattern. All serum samples contained significant amounts of ACA determined by enzyme linked immunosorbent assay. These Antibodies were detected in only 4% of HTLV-I seropositive SS patients but were present in 19.9% of HTLV-I seronegative SS patients. Furthermore, the prevalences of anti-SS-A/Ro and anti-SS-B/La Antibodies in serum samples of ACA positive patients were significantly lower than those in ACA negative SS patients. CONCLUSION These results suggest that SS patients with anti-SS-A/Ro or anti-SS-B/La Antibodies, or both, might be aetiopathologically distinct from SS patients with ACA. HTLV-I might be involved in the pathogenesis of SS in a subset of patients with anti-SS-A/Ro or anti-SS-B/La Antibodies, or both, but not SS patients with ACA.
X Bossuyt - One of the best experts on this subject based on the ideXlab platform.
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Anti-PM/Scl-100 and anti-RNA-polymerase III Antibodies in scleroderma
Clinica Chimica Acta, 2010Co-Authors: L Maes, D Blockmans, P Verschueren, R Westhovens, K Op De Beéck, P Vermeersch, K Van Den Bergh, R W Burlingame, M Mahler, X BossuytAbstract:Abstract Background Systemic sclerosis (SSc) is a rare autoimmune disease characterized by the presence of various autoAntibodies, including Anti-Centromere, anti-topoisomerase (Scl-70), anti-PM/Scl-100, and anti-RNA-polymerase III (RNA Pol-III) Antibodies. Recently, new ELISA based immunoassays have become available for the detection of anti-PM/Scl and anti-RNA Pol-lII Antibodies. Objective We studied the prevalence and clinical association of anti-PM/Scl-100 (PM1-Alpha) and anti-RNA Pol-III Antibodies. Methods Antibodies to PM1-Alpha and RNA Pol-III were measured by ELISA (DR. Fooke Laboratories and Inova Diagnostics, respectively) in 242 patients with various connective tissue diseases (CTD) (including 70 SSc patients) and in 36 non-CTD controls. Results Low levels of PM1-Alpha Antibodies were found in various CTDs, whereas high levels were exclusively found in SSc, dermatomyositis and polymyositis, albeit at low frequency (4.7%). Anti-RNA Pol-III Antibodies were found in 7% of SSc and in 1% of non-CTD and CTD controls. Anti-Centromere and anti-Scl-70 Antibodies were found in 37% and 21% of SSc patients, respectively. Anti-Centromere Antibodies were associated with limited cutaneous SSc and anti-Scl-70 Antibodies with diffuse cutaneous SSc and interstitial lung disease. Because of the low number of samples positive for anti-PM/Scl-100 or RNA Pol-III Antibodies, no clinical feature was statistically correlated with the presence of either reactivity, but taken together the presence of either antibody was correlated with interstitial lung disease. Anti-PM1-Alpha and anti-RNA Pol-III Antibodies were mutually exclusive with anti-Scl-70 Antibodies. Conclusions At high levels, anti-PM/Scl-100 Antibodies were associated with SSc, PM, and DM, albeit at low frequency. Anti-RNA Pol-III Antibodies were associated with SSc (in 7%) with high specificity.
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Anti-PM/Scl-100 and anti-RNA-polymerase III Antibodies in scleroderma.
Clinica chimica acta; international journal of clinical chemistry, 2010Co-Authors: L Maes, D Blockmans, P Verschueren, R Westhovens, K Op De Beéck, P Vermeersch, K Van Den Bergh, R W Burlingame, M Mahler, X BossuytAbstract:Systemic sclerosis (SSc) is a rare autoimmune disease characterized by the presence of various autoAntibodies, including Anti-Centromere, anti-topoisomerase (Scl-70), anti-PM/Scl-100, and anti-RNA-polymerase III (RNA Pol-III) Antibodies. Recently, new ELISA based immunoassays have become available for the detection of anti-PM/Scl and anti-RNA Pol-lII Antibodies. We studied the prevalence and clinical association of anti-PM/Scl-100 (PM1-Alpha) and anti-RNA Pol-III Antibodies. Antibodies to PM1-Alpha and RNA Pol-III were measured by ELISA (DR. Fooke Laboratories and Inova Diagnostics, respectively) in 242 patients with various connective tissue diseases (CTD) (including 70 SSc patients) and in 36 non-CTD controls. Low levels of PM1-Alpha Antibodies were found in various CTDs, whereas high levels were exclusively found in SSc, dermatomyositis and polymyositis, albeit at low frequency (4.7%). Anti-RNA Pol-III Antibodies were found in 7% of SSc and in 1% of non-CTD and CTD controls. Anti-Centromere and anti-Scl-70 Antibodies were found in 37% and 21% of SSc patients, respectively. Anti-Centromere Antibodies were associated with limited cutaneous SSc and anti-Scl-70 Antibodies with diffuse cutaneous SSc and interstitial lung disease. Because of the low number of samples positive for anti-PM/Scl-100 or RNA Pol-III Antibodies, no clinical feature was statistically correlated with the presence of either reactivity, but taken together the presence of either antibody was correlated with interstitial lung disease. Anti-PM1-Alpha and anti-RNA Pol-III Antibodies were mutually exclusive with anti-Scl-70 Antibodies. At high levels, anti-PM/Scl-100 Antibodies were associated with SSc, PM, and DM, albeit at low frequency. Anti-RNA Pol-III Antibodies were associated with SSc (in 7%) with high specificity. Copyright 2010 Elsevier B.V. All rights reserved.
Luc Mouthon - One of the best experts on this subject based on the ideXlab platform.
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Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease
Chest, 2011Co-Authors: David Launay, Yannick Allanore, Olivier Bletry, Marc Humbert, Alice Berezne, Vincent Cottin, Louis-jean Couderc, Azzedine Yaïci, Pierre-yves Hatron, Luc MouthonAbstract:Background: Pulmonary hypertension (PH) complicating systemic sclerosis (SSc)-related interstitial lung disease (ILD) is usually associated with a poor prognosis. However, data are either lacking or scarce on prognostic factors in this condition. The objectives of this study were to compare the survival of patients with ILD-associated PH (PH-ILD) or pulmonary arterial hypertension (PAH) and to determine whether the severity of PH has prognostic value in SSc-associated PH-ILD. Methods: Consecutive patients with SSc and PH-ILD (n = 47) or PAH (n = 50) confirmed by rightsided heart catheterization were included in a cross-sectional analysis. PH was classified as mild (mean pulmonary arterial pressure [mPAP] 35 mm Hg). Results: As compared with patients with PAH, subjects with PH-ILD were younger, were more frequently men with a history of smoking, had more frequently diffuse SSc, less frequently Anti-Centromere Antibodies, and a lower FVC/diffusing capacity of lung for carbon monoxide (DLCO) ratio. They had a worse prognosis than patients with PAH (3-year survival of 47% vs 71%, respectively; P=.07). Patients with mild PH-ILD had similar poor outcomes when compared with those with moderate to severe PH-ILD. Pericardial effusion (hazard ratio [HR], 2.44; P=.04) and lower DLCO (HR, 0.96; P=.01) were the only independent factors predictive of a poor survival in the PH-ILD group. Conclusions: Patients with SSc with PH-ILD had a different phenotype and a worse prognosis than those with SSc and PAH. Lower DLCO and presence of pericardial effusion were predictive of a poor outcome in PH-ILD, whereas mPAP seemed to have no prognostic significance. CHEST 2011; 140(4):1016-1024
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New insights into the pathogenesis of systemic sclerosis.
Autoimmunity reviews, 2003Co-Authors: Mathieu C. Tamby, Youri Chanseaud, Loïc Guillevin, Luc MouthonAbstract:Systemic sclerosis (SSc) is a connective tissue disorder characterized by vascular abnormalities and excessive collagen synthesis. Extracellular matrix overproduction by fibroblasts results from abnormal interactions among endothelial cells, mononuclear cells (lymphocytes and monocytes) and fibroblasts, in a setting of vascular hyperreactivity and tissue hypoxia. Many autoAntibodies have been identified in the sera of SSc patients; some of them are specific to the disease, such as Anti-Centromere Antibodies in limited SSc, anti-topoisomerase 1 and anti-RNA polymerase I/III Antibodies in diffuse SSc. Their pathogenetic role(s) remains uncertain. However, genetic, environmental and possibly alloreactive factors might also contribute to disease susceptibility.
D Blockmans - One of the best experts on this subject based on the ideXlab platform.
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Anti-PM/Scl-100 and anti-RNA-polymerase III Antibodies in scleroderma
Clinica Chimica Acta, 2010Co-Authors: L Maes, D Blockmans, P Verschueren, R Westhovens, K Op De Beéck, P Vermeersch, K Van Den Bergh, R W Burlingame, M Mahler, X BossuytAbstract:Abstract Background Systemic sclerosis (SSc) is a rare autoimmune disease characterized by the presence of various autoAntibodies, including Anti-Centromere, anti-topoisomerase (Scl-70), anti-PM/Scl-100, and anti-RNA-polymerase III (RNA Pol-III) Antibodies. Recently, new ELISA based immunoassays have become available for the detection of anti-PM/Scl and anti-RNA Pol-lII Antibodies. Objective We studied the prevalence and clinical association of anti-PM/Scl-100 (PM1-Alpha) and anti-RNA Pol-III Antibodies. Methods Antibodies to PM1-Alpha and RNA Pol-III were measured by ELISA (DR. Fooke Laboratories and Inova Diagnostics, respectively) in 242 patients with various connective tissue diseases (CTD) (including 70 SSc patients) and in 36 non-CTD controls. Results Low levels of PM1-Alpha Antibodies were found in various CTDs, whereas high levels were exclusively found in SSc, dermatomyositis and polymyositis, albeit at low frequency (4.7%). Anti-RNA Pol-III Antibodies were found in 7% of SSc and in 1% of non-CTD and CTD controls. Anti-Centromere and anti-Scl-70 Antibodies were found in 37% and 21% of SSc patients, respectively. Anti-Centromere Antibodies were associated with limited cutaneous SSc and anti-Scl-70 Antibodies with diffuse cutaneous SSc and interstitial lung disease. Because of the low number of samples positive for anti-PM/Scl-100 or RNA Pol-III Antibodies, no clinical feature was statistically correlated with the presence of either reactivity, but taken together the presence of either antibody was correlated with interstitial lung disease. Anti-PM1-Alpha and anti-RNA Pol-III Antibodies were mutually exclusive with anti-Scl-70 Antibodies. Conclusions At high levels, anti-PM/Scl-100 Antibodies were associated with SSc, PM, and DM, albeit at low frequency. Anti-RNA Pol-III Antibodies were associated with SSc (in 7%) with high specificity.
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Clinical and serological evaluation of a novel CENP-A peptide based ELISA
Arthritis research & therapy, 2010Co-Authors: Michael Mahler, D Blockmans, R Westhovens, Liesbeth Maes, Xavier Bossuyt, Gabriela Riemekasten, Sandra Schneider, Falk Hiepe, Andreas Swart, Irmgard GürtlerAbstract:Introduction Anti-Centromere Antibodies (ACA) are useful biomarkers in the diagnosis of systemic sclerosis (SSc). ACA are found in 20 to 40% of SSc patients and, albeit with lower prevalence, in patients with other systemic autoimmune rheumatic diseases. Historically, ACA were detected by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed by immunoassays using recombinant CENP-B. The objective of this study was to evaluate a novel CENP-A peptide ELISA.
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Anti-PM/Scl-100 and anti-RNA-polymerase III Antibodies in scleroderma.
Clinica chimica acta; international journal of clinical chemistry, 2010Co-Authors: L Maes, D Blockmans, P Verschueren, R Westhovens, K Op De Beéck, P Vermeersch, K Van Den Bergh, R W Burlingame, M Mahler, X BossuytAbstract:Systemic sclerosis (SSc) is a rare autoimmune disease characterized by the presence of various autoAntibodies, including Anti-Centromere, anti-topoisomerase (Scl-70), anti-PM/Scl-100, and anti-RNA-polymerase III (RNA Pol-III) Antibodies. Recently, new ELISA based immunoassays have become available for the detection of anti-PM/Scl and anti-RNA Pol-lII Antibodies. We studied the prevalence and clinical association of anti-PM/Scl-100 (PM1-Alpha) and anti-RNA Pol-III Antibodies. Antibodies to PM1-Alpha and RNA Pol-III were measured by ELISA (DR. Fooke Laboratories and Inova Diagnostics, respectively) in 242 patients with various connective tissue diseases (CTD) (including 70 SSc patients) and in 36 non-CTD controls. Low levels of PM1-Alpha Antibodies were found in various CTDs, whereas high levels were exclusively found in SSc, dermatomyositis and polymyositis, albeit at low frequency (4.7%). Anti-RNA Pol-III Antibodies were found in 7% of SSc and in 1% of non-CTD and CTD controls. Anti-Centromere and anti-Scl-70 Antibodies were found in 37% and 21% of SSc patients, respectively. Anti-Centromere Antibodies were associated with limited cutaneous SSc and anti-Scl-70 Antibodies with diffuse cutaneous SSc and interstitial lung disease. Because of the low number of samples positive for anti-PM/Scl-100 or RNA Pol-III Antibodies, no clinical feature was statistically correlated with the presence of either reactivity, but taken together the presence of either antibody was correlated with interstitial lung disease. Anti-PM1-Alpha and anti-RNA Pol-III Antibodies were mutually exclusive with anti-Scl-70 Antibodies. At high levels, anti-PM/Scl-100 Antibodies were associated with SSc, PM, and DM, albeit at low frequency. Anti-RNA Pol-III Antibodies were associated with SSc (in 7%) with high specificity. Copyright 2010 Elsevier B.V. All rights reserved.
