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001-es BibID:BIBFORM078908
Első szerző:Betteridge, Zoe
Cím:Clinical Phenotypes of Caucasian Adult and Juvenile Dermatomyositis Patients with Anti-MDA5 Autoantibodies / Zoe Betteridge, Sarah Tansley, Harsha Gunawardena, Lucy R. Wedderburn, Hector Chinoy, Robert G. Cooper, Jiri Vencovsky, Lenka Plestilova, Ingrid E. Lundberg, Katalin Danko, Melinda Vincze, Neil McHugh, UK JDRG, EuMyoNet
Dátum:2019
Megjegyzések:Background/Purpose: Autoantibodies to MDA5 have been previously reported in Japanese patients with dermatomyositis (DM) and are associated with clinically-amyopathic DM and rapidly progressing interstitial lung disease (ILD). These autoantibodies also occur in juvenile Japanese DM patients in association with ILD. Anti-MDA5 has also been reported in a cohort of mixed ethnicity, where it was found to be associated with ILD and severe vasculopathy. Here we report on the frequency and clinical manifestations of anti-MDA5 autoantibodies in a large international multicenter cohort of Caucasian adult and juvenile myositis patients. Methods: Serum was available from 1331 adult myositis patients (480 DM) recruited to the EuMyoNet repository and 172 JDM patients recruited to the UK JDRG. Sera were screened for autoantibodies by immunoprecipitation (IPP) using radio-labelled K562 cell extract. Sera with immunoprecipitates at approximately 140 kDa were tested for anti-MDA5 autoantibodies by ELISA using recombinant MDA5 (Cambridge BioSciences). Clinical data were collected on standardised proformas. Sera from 169 systemic sclerosis, 40 SLE and 50 healthy controls were also analyzed by IPP. Statistical analysis was performed using SPSS and Fishers Exact Test. Results: Anti-MDA5 autoantibodies were found in the sera of 12 JDM patients and 25 adults. The frequency in the JDM cohort was 7.0%, in comparison to 1.9% in the overall adult myositis population and 3.8% in the adult DM group. Anti-MDA5 autoantibodies were not found in any patients with PM or any control sera. As with previous reports, there was an association between ILD and anti-MDA5 (p_0.044) in the adultDMpatients. However, contrary to previous reports, this was not seen to be rapidly progressing, with no known ILD related fatalities in the anti-MDA5 positive group. In comparison, ILD was not found to be a significant association in the JDM anti-MDA5 positive group, with no patients having ILD reported as a clinical manifestation. Similarly to previous report, anti-MDA5 positive patients had significantly more ulceration (skin: p_0.047 and mouth: p_0.039), in the JDM cohort, compared with the anti-MDA5 negative group. Whilst ulceration data was unavailable in the adult population, the presence of anti-MDA5 was significantly associated with Gottron's papules (p_0.001). Conclusion: We report the presence of anti-MDA5 autoantibodies in a large cohort of Caucasian JDM and adult myositis patients. The frequency of anti-MDA5 autoantibodies varies between adults and children, along with differences in the clinical profile. As with previous reports, the presence of anti-MDA5 is associated with the presence of severe cutaneous features in both JDM and adults. However, in this study ILD was only an association in the adult population, suggesting differences in pathogenesis or aetiology. This study also highlights differences in clinical manifestations between different ethnic groups, with the ILD in our adult patients being
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
Megjelenés:Arthritis & Rheumatism. - 64 : 10 (2019), p. S715. -
További szerzők:Tansley, Sarah Gunawardena, Harsha Wedderburn, Lucy R. Chinoy, Hector Cooper, Robert G. Vencovsky, Jiri Plestilova, Lenka Lundberg, Ingrid Dankó Katalin (1952-2021) (belgyógyász, allergológus és klinikai immunológus) Nagy-Vincze Melinda (1985-) (orvos) McHugh, Neil UK JDRG EuMyoNet
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2.

001-es BibID:BIBFORM078900
035-os BibID:(PMID)30992170
Első szerző:Betteridge, Zoe
Cím:Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients / Z. Betteridge, S. Tansley, G. Shaddick, H. Chinoy, R. G. Cooper, R. P. New, J. B. Lilleker, J. Vencovsky, L. Chazarain, K. Danko, M. Nagy-Vincze, L. Bodoki, M. Dastmalchi, L. Ekholm, I. E. Lundberg, N. McHugh, UKMyonet contributors
Dátum:2019
ISSN:0896-8411
Megjegyzések:OBJECTIVES: To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. METHODS: Adult patients with confirmed IIM recruited to the EuroMyositis registry (n?=?1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. RESULTS: MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2-7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p?<?0.001) with cutaneous involvement. Anti-TIF1 and anti-Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti-SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti-tRNA synthetases, anti-MDA5, and anti-U1RNP/Sm. Overlap disease was strongly associated with anti-PMScl, anti-Ku, anti-U1RNP/Sm and anti-Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations. CONCLUSIONS: Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Autoantibodies
Autoimmune
Dermatomyositis
Myositis
Polymyositis
Megjelenés:Journal Of Autoimmunity. - 101 (2019), p. 48-55. -
További szerzők:Tansley, Sarah Shaddick, G. Chinoy, Hector Cooper, Robert G. New, Robert Paul Lilleker, James B. Vencovsky, Jiri Chazarain, L. Dankó Katalin (1952-2021) (belgyógyász, allergológus és klinikai immunológus) Nagy-Vincze Melinda (1985-) (orvos) Bodoki Levente (1986-) (PhD hallgató) Dastmalchi, Maryam Ekholm, L. Lundberg, Ingrid McHugh, Neil UKMyonet contributors
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DOI
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3.

001-es BibID:BIBFORM040271
Első szerző:Chinoy, Hector
Cím:Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies : a European-wide case study / Chinoy H., Adimulam S., Marriage F., New P., Vincze M., Zilahi E., Kapitány A., Gyetvai A., Ekholm L., Novota P., Remakova M., Charles P., McHugh N. J., Padyukov L., Alfredsson L., Vencovsky J., Lundberg I. E., Danko K., Ollier W. E., Cooper R. G.
Dátum:2012
Megjegyzések:Objectives: HLA-DRB1*03 is strongly associated withanti-Jo-1-positive idiopathic infl ammatory myopathies (IIM)and there is now increasing evidence that Jo-1 antigen ispreferentially expressed in lung tissue. This study examinedwhether smoking was associated with the development ofanti-Jo-1 antibodies in HLA-DRB1*03-positive IIM.Methods IIM cases were selected with concurrentinformation regarding HLA-DRB1 status, smoking historyand anti-Jo-1 antibody status. DNA was genotypedat DRB1 using a commercial sequence-specifi coligonucleotide kit. Anti-Jo-1 antibody status wasestablished using a line blot assay or immunoprecipitation.Results 557 Caucasian IIM patients were recruited fromHungary (181), UK (99), Sweden (94) and Czech Republic(183). Smoking frequency was increased in anti-Jo-1-positive IIM cases, and reached statistical signifi cance inHungarian IIM (45% Jo-1-positive vs 17% Jo-1-negative,OR 3.94, 95% CI 1.53 to 9.89, p<0.0001). A strongassociation between HLA-DRB1*03 and anti-Jo-1status was observed across all four cohorts (DRB1*03frequency: 74% Jo-1-positive vs 35% Jo-1-negative, OR5.55, 95% CI 3.42 to 9.14, p<0.0001). The frequency ofHLA-DRB1*03 was increased in smokers. The frequencyof anti-Jo-1 was increased in DRB1*03-positive smokersvs DRB1*03-negative non-smokers (42% vs 8%, OR 7.75,95% CI 4.21 to 14.28, p<0.0001) and DRB1*03-positivenon-smokers (42% vs 31%, p=0.08). In DRB1*03-negative patients, anti-Jo-1 status between smokers andnon-smokers was not signifi cantly different. No signifi cantinteraction was noted between smoking and DRB1*03status using anti-Jo-1 as the outcome measure.Conclusion Smoking appears to be associated withan increased risk of possession of anti-Jo-1 in HLADRB1*03-positive IIM cases. The authors hypothesisethat an interaction between HLA-DRB1*03 and smokingmay prime the development of anti-Jo-1 antibodies.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
myopathy
Megjelenés:Annals of the Rheumatic Diseases 71 : 6 (2012), p. 961-965. -
További szerzők:Adimulam, S. Marriage, F. New, Paul Nagy-Vincze Melinda (1985-) (orvos) Zilahi Erika (1964-) (molekuláris biológus) Kapitány Anikó (1979-) (molekuláris biológus) Gyetvai Ágnes Ekholm, L. Novota, P. Remakova, M. Charles, Peter McHugh, Neil Padyukov, Leonid Alfredsson, Lars Vencovsky, Jiri Lundberg, Ingrid Dankó Katalin (1952-2021) (belgyógyász, allergológus és klinikai immunológus) Ollier, William E. Cooper, Robert G.
Internet cím:DOI
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