C Bunn
Royal Free Hospital
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Featured researches published by C Bunn.
Gut | 2006
Cristina Rigamonti; Lynne Shand; Maurille Feudjo; C Bunn; Carol M. Black; Christopher P. Denton; Andrew K. Burroughs
Backgrounds and aims: To evaluate the prognosis of primary biliary cirrhosis (PBC) together with systemic sclerosis (SSc), as this is unknown. Methods and results: A PBC database of 580 patients identified 43 with PBC and SSc: two patients with PBC alone were matched to each PBC-SSc patient for serum bilirubin concentration at the initial visit. Forty (93%) patients had limited cutaneous SSc. At diagnosis of PBC, median values were: 49.7 years, bilirubin 17 μmol/l, and albumin 40.5 g/l. Liver diagnosis occurred a median 4.9 years after SSc in 24 (56%) patients. In matched patients, median values at diagnosis were: 53.2 years, bilirubin 12 μmol/l, and albumin 41 g/l. Median follow up was similar: 3.16 years (PBC-SSc) and 4.8 years (PBC alone). The risk of transplantation or death from diagnosis, adjusting for sex, age, log bilirubin, and alkaline phosphatase was significantly lower in PBC-SSc (hazard ratio 0.116, p = 0.01) due to less transplantation (hazard ratio 0.068, p = 0.006). The rate of bilirubin increase was less in PBC-SSc (p = 0.04). Overall survival was similar (hazard ratio 1.11, p = 0.948); there were nine deaths (21%) in PBC-SSc (six SSc related and two liver related) and nine (11%) in PBC alone (six liver related). Conclusions: Liver disease has a slower progression in PBC-SSc compared with matched patients with PBC alone.
Genes and Immunity | 2001
Fc Gilchrist; C Bunn; Pj Foley; Penelope A. Lympany; Carol M. Black; Kenneth I. Welsh; Rm du Bois
Scleroderma is a condition of variable phenotype characterised by fibrosis of the skin and internal organs. There is a range of disease-specific autoantibodies found in the sera of patients. The aims of this study were to: (1) investigate the role of the MHC and particularly HLA-DP in the production of autoantibodies; (2) investigate clinical associations with autoantibodies. We have performed HLA class II typing using PCR with sequence-specific primers on DNA samples from 202 scleroderma patients and 307 UK control subjects. All patients had well defined clinical phenotypes. Sera from patients were examined for the presence of disease specific autoantibodies in particular the anti-topoisomerase autoantibody (ATA), the anti-centromere autoantibody (ACA) and the anti-RNA polymerase autoantibody (ARA). There was a striking association between HLA-DPB1*1301 and ATA (Pcorr = 0.0001). In addition, ATA was associated with HLA-DRB1*11 and the anticentromere autoantibody (ACA) with HLA-DRB1*04, HLA-DRB1*08 (P = 0.001) and HLA-DQB1 alleles with a glycine residue at position 26. Very strong associations were detected between clinical phenotypes and autoantibodies. ATA was associated with pulmonary fibrosis (P = 0.00002), anti-RNA polymerase autoantibody (ARA) with renal involvement (P = 0.0000006) and diffuse skin disease (P = 0.00001), and ACA with limited skin involvement (P = 0.00002) and protection against pulmonary fibrosis (P = 0.0000003). We have identified a significant association between the ATA and HLA-DPB1*1301 which may provide an insight into how this autoantibody is formed. Patient clinical characteristics depend on the autoantibodies they carry.
Rheumatology | 2009
Svetlana I. Nihtyanova; Jennifer C Parker; Carol M. Black; C Bunn; Christopher P. Denton
OBJECTIVES Anti-RNA-polymerase antibodies (ARAs) are associated with the diffuse cutaneous subset of SSc (dcSSc) and particularly with scleroderma renal crisis (SRC). We analysed serial ARA levels and explored the relationship with clinical features and disease outcome. METHODS A commercially available ELISA method with a recombinant peptide of RNA polymerase III was used and ARA levels were measured in a well-characterized cohort of SSc cases. RESULTS ARA levels were measured in 64 SSc patients. Of them, 78% (n = 50) were females and 92% (n = 59) had dcSSc, 39% (n = 25) had SRC, 20% (n = 13) had pulmonary fibrosis (PF), 9% (n = 6) had pulmonary arterial hypertension and 3% (n = 2) had cardiac involvement. There was considerable inter- and intra-patient variability in ARA levels (11-210 U/ml). There was no correlation between absolute ARA levels (at baseline or throughout the disease course) and outcome. There was a moderate correlation between time to peak ARA level and development of significant PF (Pearson correlation = 0.669, P = 0.034), but no correlation between peak ARA levels and onset of SRC. ARA levels change correlated with change in skin score (correlation coefficient within subjects = 0.236, P = 0.011). CONCLUSIONS The pathogenic significance of ARA is unclear. Despite the very strong association of ARA with SRC, we could not show the clinically significant association between absolute levels of antibody and development of internal organ complications, which makes repeated measurements of ARA levels unnecessary. However, changes in ARA level over time occur and may reflect changes in skin score.
Journal of Autoimmune Diseases | 2009
Jennifer C Parker; Rufus W Burlingame; C Bunn
BackgroundAntibodies against Ro-52 have been described in patients with a broad spectrum of autoimmune disease, most commonly in association with anti-Ro-60 in systemic lupus erythematosus and Sjogrens syndrome. However, in inflammatory myositis anti-Ro-52 is frequently present without anti-Ro-60 and is closely linked to the presence of aminoacyl-tRNA synthetase (aats) antibodies. To date there have been no comprehensive reports on the frequency of anti-Ro-52 in systemic sclerosis (SSc), a disease characterised by hallmark autoantibodies that occur in non-overlapping subsets. Clinically, each antibody-defined group has a distinct pattern of organ involvement, some featuring myositis.ObjectivesTo determine the frequency of anti-Ro-52 in serologically defined groups of SSc patients and to investigate a possible link with myositis-associated autoantibodies.MethodsSerum samples from 1010 patients with SSc and 55 and 32 patients with anti-aats and anti-Ku respectively were tested for the presence of anti-Ro-52 using a commercial ELISA.ResultsThe prevalence of anti-Ro-52 was 15–38% in nine of the eleven sub-groups. There were no significant differences in mean anti-Ro-52 levels in these groups with the exception of that defined by the presence of anti-U1-RNP. In the remaining groups defined by anti-Ro-60 and anti-aats, anti-Ro-52 was present in 92% and 100% respectively. In sera from non-SSc patients with anti-aats, anti-Ro-52 was detected in 64%.ConclusionAnti-Ro-52 is present throughout the SSc population. It is neither more prevalent in the myositis-associated antibody groups nor does it segregate with any other major SSc-specific autoantibodies. The co-existence of anti-Ro-52 with both anti-Ro-60 and anti-aats is confirmed.
Rheumatology | 2008
Jennifer C Parker; R. W. Burlingame; T. T. Webb; C Bunn
Objectives. To evaluate the analytical performance of an ELISA for the detection of anti-RNA polymerase III antibody (ARA) and to assess IIF as a method for identifying this antibody. Methods. A commercially available ELISA was used to assess the presence of ARA in sera from 1018 SSc patients. The sera had been divided into sub-populations based on the presence of specific autoantibodies, ANA pattern or the absence of both. Patients with ARA (n = 209) had been identified by characteristic ANA pattern by IIF on HEp-2 cell substrate [and additionally by radio-immunoprecipitation (IP) in 157/209 cases]. The remaining 809 SSc patients acted as a control group. Results. Of 157 patients in whom ARA had been confirmed by IP, 150 were positive by ELISA providing a sensitivity of 96%. In the group where ARA had only been assessed by IIF, 100% (52/52) were ELISA positive. The ANA patterns indicating the presence of ARA were a fine-speckled nucleoplasmic stain with additional occasional bright dots, with or without concurrent punctate nucleolar staining. In the SSc control group, the ELISA attained a specificity of 98%, ARA being detected in 17/809 patients. Conclusions. We report the outcome of a study on a large population of SSc patients that shows the ARA ELISA to be of high analytical sensitivity and specificity. We confirm that there is minimal overlap between ARA and other SSc-specific autoantibodies. Additionally, it is demonstrated that the presence of ARA correlates with identifiable patterns by IIF on HEp-2 cell substrate.
Journal of Clinical Pathology | 2011
Jennifer C Parker; C Bunn
Aim To evaluate the sensitivity of a commercial autoantibody screening method (Phadia EliA connective tissue disease (CTD) screen) for the detection of less common antibody specificities associated with connective tissue disease. Methods 399 sera positive for anti-PM/Scl (n=102), anti-RNA polymerase III (n=199), anti-fibrillarin (n=50), anti-Mi-2 (n=12), anti-proliferating cell nuclear antigen (PCNA) (n=13) and anti-ribosomal P (n=23) were analysed using the solid phase assay. Each well was coated with the respective antigens for these autoantibodies and also with the antigens Ro, La, Jo-1, Scl-70, CENP-B, U1-RNP, Sm and native DNA. Results All the anti-ribosomal P, anti-PCNA and anti-Mi-2 sera and 94% of the anti-PM/Scl sera were positive. For anti-fibrillarin, 36 (68%) were positive and 12 (22%) were equivocal. For anti-RNA polymerase III, 131 (67%) were positive, 23 (11%) were equivocal and 45 (22%) were negative. Conclusions The sensitivity of the Phadia EliA CTD screen is currently insufficient for the assay to be used as a screening test for anti-fibrillarin and anti-RNA polymerase III, but appears to be satisfactory for the other autoantibodies tested.
Arthritis & Rheumatism | 2016
Zoe Betteridge; Felix Woodhead; Hui Lu; Gavin Shaddick; C Bunn; Christopher P. Denton; David J. Abraham; Roland M. du Bois; Mervyn Lewis; Athol U. Wells; Neil McHugh
To investigate novel systemic sclerosis (SSc) autoantibodies in autoantibody‐negative patients and establish clinical associations.
Gut | 2011
David G. Walker; A S Bancil; Hrt Williams; C Bunn; Timothy R. Orchard
Introduction Atypical perinuclear antineutrophil cytoplasmic antibody (pANCA), anti-Saccharomyces cerevisiae antibody (ASCA) and more recently Outer Membrane Porin C (Omp-C) have been extensively studied in European and North American IBD populations. There is emerging evidence that the combination of these autoantibodies may increase the accuracy of diagnosis in IBD, however it is not known how reliable these markers are in IBD patients of different ethnicities. The aims of this study were to first determine the prevalence of ASCA, Omp-C and atypical pANCA in Indian Asian IBD patients and controls. The second aim was to determine the ability of ASCA and atypical pANCA to discriminate between CD and UC in Indian Asians. Methods A total of 191 Indian Asian IBD patients (UC 139, CD 52) and 36 healthy ethnically matched controls were included in the study. Sera were analysed for the presence of ASCA IgA and IgG and Omp-C antibodies using a commercially available ELISA (Quanta Lite; INOVA Diagnostics). To test for atypical pANCA, indirect immunofluorescence was performed on sera diluted 1/10 and tested on ethanol fixed neutrophil substrate (INOVA diagnostics) using FITC-conjugated rabbit antihuman IgG. Sensitivity and specificity were estimated for each serological marker and the relationship between disease phenotype and serological positivity was tested using the χ2 test. Results Accuracy of the serological markers ASCA (IgA or IgG isotypes) and Omp-C for differentiation of healthy controls from those with CD showed a sensitivity of 50% and 54% but a higher specificity (75% and 78%). The sensitivity and specificity of pANCA was calculated for differentiating UC from controls as 48% and 97% respectively. The combination of ASCA-/pANCA+ resulted in better diagnostic accuracy for differentiating CD from UC (sensitivity 32% and specificity 92%) than either test alone. There was no significant association with atypical pANCA and UC phenotype (p=0.58). Both ASCA and Omp-C positivity correlated with small bowel involvement in CD patients (p=0.01 and p=0.04 respectively). Conclusion The low sensitivity of ASCA, Omp-C and pANCA limits their use for IBD screening in Indian Asian populations but the high specificity of combining ASCA and ANCA can be helpful in differentiating between UC and CD in this ethnic group. The reported sensitivities and specificities of ASCA, Omp-C and pANCA in Indian Asians are similar to those observed in Caucasian populations. In addition, the association of ASCA and Omp-C with CD phenotype has also been reported in Caucasian CD patients suggesting similar pathological mechanisms in both ethnic groups.
Rheumatology | 1998
C Bunn; Christopher P. Denton; Xu Shiwen; C Knight; Carol M. Black
Arthritis & Rheumatism | 2000
Elisabetta Renzoni; P. A. Lympany; Piersante Sestini; Panagiotis Pantelidis; Athol U. Wells; Carol M. Black; Ken I. Welsh; C Bunn; Chris Knight; Patrick J. Foley; R M du Bois