Anti-RNA polymerase III antibody-associated scleroderma renal crisis in a patient with limited cutaneous systemic sclerosis: A case report

2016 ◽  
Vol 28 (2) ◽  
pp. 369-372
Author(s):  
Daisuke Takada ◽  
Junichi Hoshino ◽  
Koichi Kikuchi ◽  
Junko Yabuuchi ◽  
Yuta Kogure ◽  
...  
Keyword(s):  
Case Report ◽  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Polymerase Iii ◽  
Renal Crisis

Analysis of Anti-RNA Polymerase III Antibody-positive Systemic Sclerosis and Altered GPATCH2L and CTNND2 Expression in Scleroderma Renal Crisis

2020 ◽  
Vol 47 (11) ◽  
pp. 1668-1677
Author(s):  
Edward P. Stern ◽  
Sandra G. Guerra ◽  
Harry Chinque ◽  
Vanessa Acquaah ◽  
David González-Serna ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Renal Biopsy ◽  
Genetic Susceptibility ◽  
Rna Polymerase Iii ◽  
Human Kidney ◽  
Scleroderma Renal Crisis ◽  
Nucleotide Polymorphisms ◽  
Polymerase Iii ◽  
Renal Crisis

ObjectiveScleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) strongly associated with anti-RNA polymerase III antibody (ARA) autoantibodies. We investigated genetic susceptibility and altered protein expression in renal biopsy specimens in ARA-positive patients with SRC.MethodsARA-positive patients (n = 99) with at least 5 years’ follow-up (49% with a history of SRC) were selected from a well characterized SSc cohort (n = 2254). Cases were genotyped using the Illumina Human Omni-express chip. Based on initial regression analysis, 9 single-nucleotide polymorphisms (SNP) were chosen for validation in a separate cohort of 256 ARA-positive patients (40 with SRC). Immunostaining of tissue sections from SRC or control kidney was used to quantify expression of candidate proteins based upon genetic analysis of the discovery cohort.ResultsAnalysis of 641,489 SNP suggested association of POU2F1 (rs2093658; P = 1.98 × 10−5), CTNND2 (rs1859082; P = 5.58 × 10−5), HECW2 (rs16849716; P = 1.2 × 10−4), and GPATCH2L (rs935332; P = 4.92 × 10−5) with SRC. Further, the validation cohort showed an association between rs935332 within the GPATCH2L region, with SRC (P = 0.025). Immunostaining of renal biopsy sections showed increased tubular expression of GPATCH2L (P = 0.026) and glomerular expression of CTNND2 (P = 0.026) in SRC samples (n = 8) compared with normal human kidney controls (n = 8), despite absence of any genetic replication for the associated SNP.ConclusionIncreased expression of 2 candidate proteins, GPATCH2L and CTNND2, in SRC compared with control kidney suggests a potential role in pathogenesis of SRC. For GPATCH2L, this may reflect genetic susceptibility in ARA-positive patients with SSc based upon 2 independent cohorts.

scholarly journals Prevalence, Correlates and Outcomes of Gastric Antral Vascular Ectasia in Systemic Sclerosis: A EUSTAR Case-control Study

2013 ◽  
Vol 41 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Etienne Ghrénassia ◽  
Jérome Avouac ◽  
Dinesh Khanna ◽  
Chris T. Derk ◽  
Oliver Distler ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Gastric Antral Vascular Ectasia ◽  
Vascular Ectasia ◽  
Polymerase Iii ◽  
European League Against Rheumatism ◽  
Vascular Phenotype ◽  
Renal Crisis

Objective.To estimate the prevalence, determine the subgroups at risk, and the outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular ectasia (GAVE).Methods.We queried the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients with SSc-GAVE. Each case was matched for cutaneous subset and disease duration with 2 controls with SSc recruited from the same center, evaluated at the time the index case made the diagnosis of GAVE. SSc characteristics were recorded at the time GAVE occurred and the last observation was collected to define the outcomes.Results.Forty-nine patients with SSc and GAVE were included (24 with diffuse cutaneous SSc) and compared to 93 controls with SSc. The prevalence of GAVE was estimated at about 1% of patients with SSc. By multivariate analysis, patients with SSc-GAVE more frequently exhibited a diminished (< 75%) DLCO value (OR 12.8; 95% CI 1.9–82.8) despite less frequent pulmonary fibrosis (OR 0.2; 95% CI 0.1–0.6). GAVE was also associated with the presence of anti-RNA-polymerase III antibodies (OR 4.6; 95% CI 1.2–21.1). SSc-GAVE was associated with anemia (82%) requiring blood transfusion (45%). Therapeutic endoscopic procedures were performed in 45% of patients with GAVE. After a median followup of 30 months (range 1–113 months), survival was similar in patients with SSc-GAVE compared to controls, but a higher number of scleroderma renal crisis cases occurred (12% vs 2%; p = 0.01).Conclusion.GAVE is rare and associated with a vascular phenotype, including anti-RNA-polymerase III antibodies, and a high risk of renal crisis. Anemia, usually requiring blood transfusions, is a common complication.

scholarly journals Clinical and Immunologic Predictors of Scleroderma Renal Crisis in Japanese Systemic Sclerosis Patients With Anti-RNA Polymerase III Autoantibodies

2015 ◽  
Vol 67 (4) ◽  
pp. 1045-1052 ◽  
Author(s):  
Yasuhito Hamaguchi ◽  
Masanari Kodera ◽  
Takashi Matsushita ◽  
Minoru Hasegawa ◽  
Yuki Inaba ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Polymerase Iii ◽  
Renal Crisis

scholarly journals Analysis of anti-RNA polymerase III antibodies in Chinese Han systemic sclerosis patients

2019 ◽  
Vol 39 (4) ◽  
pp. 1191-1197 ◽  
Author(s):  
Chenxi Liu ◽  
Yong Hou ◽  
Dong Xu ◽  
Liubing Li ◽  
Yanfang Zhang ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Connective Tissue Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Chinese Han ◽  
College Hospital ◽  
Polymerase Iii ◽  
Renal Crisis

Abstract Objectives This study aimed to assess the prevalence and clinical correlation of anti-RNA polymerase III antibodies (anti-RNAP III) in Chinese Han systemic sclerosis (SSc) patients. Methods Serum samples from 236 patients with SSc, 125 patients with connective tissue diseases (CTD), and 166 healthy controls (HCs), recruited from Peking Union Medical College Hospital and 21 other medical centers in China, were tested for antibodies to RNA polymerase III by means of a line immunoassay (LIA) or an enzyme-linked immunosorbent assay (ELISA) kit. Results Anti-RNAP III antibodies were found in 14/236 SSc patients (5.93%), 1/125 (0.80%) CTD patients, and 0/166 (0.00%) HCs. The prevalence of anti-RNAP III was higher in SSc patients than in the CTD and HC groups (p = 0.02, p = 0.001, respectively). Renal crisis was significantly more common in patients with anti-RNAP III than patients without anti-RNAP III (42.9 vs. 4.1%, p < 0.0001). Gastrointestinal involvement was significantly more common in patients without anti-RNAP III than patients with anti-RNAP III (53.6 vs. 21.4%, p = 0.039). There was good agreement between the ELISA and line immunoassay (LIA) detection capabilities for anti-RNAP III. Conclusions The anti-RNAP III antibody, which was detected by ELISA, has diagnostic value for SSc and predictive value for SSc-related renal crisis. Both ELISA and LIA are very reliable methods for anti-RNAP III.Key Points• The prevalence of anti-RNAP III antibody was determined in Chinese SSc patients and performed ethnic differences.• The clinical association between anti-RNAP III antibody and Chinese SSc patients was evaluated in this research.• Methodological consistency of detection of anti-RNAP III antibody using commercial ELISA and LIA methods was evaluated in this research.

Anti-RNA Polymerase III Antibody Prevalence and Associated Clinical Manifestations in a Large Series of French Patients with Systemic Sclerosis: A Cross-sectional Study

2009 ◽  
Vol 37 (1) ◽  
pp. 125-130 ◽  
Author(s):  
OLIVIER MEYER ◽  
LUC DE CHAISEMARTIN ◽  
PASCALE NICAISE-ROLAND ◽  
JEAN CABANE ◽  
FLORENCE TUBACH ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Topoisomerase I ◽  
Rna Polymerase Iii ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
The United States ◽  
Cutaneous Disease ◽  
Polymerase Iii ◽  
Renal Crisis

Objective.To determine the prevalence of anti-RNA polymerase III autoantibodies in French patients with systemic sclerosis (SSc) and to identify the associated clinical manifestations.Methods.Consecutive patients with SSc seen in 3 tertiary centers in Paris were included. Sera samples were collected together with the relevant clinical and immunological data. Anti-RNA polymerase III antibodies were detected by ELISA at a central laboratory. Data on other antibodies were abstracted from the medical records.Results.We included 319 patients: 84% women, 36% with a diffuse cutaneous subtype, 44% with pulmonary fibrosis, 5% with pulmonary hypertension, 4% with renal crisis, among whom 29 (9.4%) had anti-RNA polymerase III antibodies. These antibodies were more prevalent in patients with diffuse than with limited cutaneous disease (14.3% vs 6.0%; OR 2.6, 95% CI 1.2–5.48, p = 0.016). Renal crisis was more prevalent in patients with than in those without anti-RNA polymerase III antibodies (14% vs 3%; OR 5.0, 95% CI 1.4–17.3, p = 0.012). Renal crisis occurred in 2.2% of patients with anti-topoisomerase I and 3.9% of patients with anticentromere antibodies. Of the patients with anti-RNA polymerase III antibodies, 24 (83%) had no other systemic sclerosis-specific autoantibodies.Conclusion.The prevalence of anti-RNA polymerase III antibodies in French patients appeared to be lower than in the United States and similar to that in continental Europe. These antibodies were consistently associated with diffuse cutaneous disease and were the most common immunological marker for renal crisis. Anti-RNA polymerase III determination can help to risk-stratify SSc patients at high risk for this severe manifestation.

scholarly journals A Unique Presentation of Anti-RNA Polymerase III Positive Systemic Sclerosis Sine Scleroderma

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Cody M. Lee ◽  
Diana Girnita ◽  
Arundhati Sharma ◽  
Surabhi Khanna ◽  
Jean M. Elwing
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Wide Spectrum ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Autoimmune Disorder ◽  
Scleroderma Renal Crisis ◽  
Polymerase Iii ◽  
Digital Ischemia ◽  
Pulmonary Arterial

Systemic sclerosis is a rare autoimmune disorder with a wide spectrum of clinical manifestations and a multitude of autoantibodies that are associated with it. In the past several years, advances in serologic testing have led to research indicating important prognostic and phenotypic associations with certain subsets of autoantibodies. In particular, anti-RNA polymerase III (anti-RNAP III) has been associated with diffuse cutaneous disease, scleroderma renal crisis, a temporal relationship with malignancy, myositis, synovitis, joint contractures, and gastric antral vascular ectasia. However, anti-RNAP III has not been associated with systemic sclerosis sine scleroderma. We describe a patient with an atypical presentation of anti-RNAP III positive systemic sclerosis sine scleroderma who presented without the typical features of anti-RNAP III disease. Instead, she presented with critical digital ischemia, pulmonary arterial hypertension, gastroesophageal reflux disease, interstitial lung disease, and no clinically detectable sclerodactyly.

scholarly journals 320. The Prognosis of Scleroderma Renal Crisis in RNA-Polymerase III Antibody-Positive Compared to Rna-Polymerase III Antibody-Negative Patients

Rheumatology ◽  
2014 ◽  
Vol 53 (suppl_1) ◽  
pp. i179-i179 ◽  
Author(s):  
Bernadette M. Lynch ◽  
Henry Penn ◽  
Jennifer Harvey ◽  
Aine Burns ◽  
Christopher P. Denton
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Polymerase Iii ◽  
Renal Crisis
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