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001-es BibID:	BIBFORM106690
035-os BibID:	(scopus)85048288877 (wos)000434672900001
Első szerző:	Parkes, Joanna E.
Cím:	Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis / Parkes Joanna E., Rothwell Simon, Oldroyd Alexander, Chinoy Hector, Lamb Janine A., Myositis Genetics Consortium (MYOGEN)
Dátum:	2018
ISSN:	1478-6354 1478-6362
Megjegyzések:	Background The prevalence of dermatomyositis (DM) versus DM and polymyositis (PM) combined has been shown to be negatively associated with latitude. This observation has been attributed to increasing exposure to ultraviolet (UV) light towards the equator. In this study, we investigated whether differing genetic background in populations could contribute to this distribution of DM. Methods Case data derived from the MYOGEN (Myositis Genetics Consortium) Immunochip study (n =?1769) were used to model the association of DM prevalence and DM-specific autoantibodies with latitude. Control data (n =?9911) were used to model the relationship of human leucocyte antigen (HLA) associated with DM autoantibodies and DM or PM single-nucleotide polymorphisms (suggestive significance in the Immunochip project, P <?2.25???10??5) in healthy control subjects with latitude. All variables were analysed against latitude using ordered logistic regression, adjusted for sex. Results The prevalence of DM, as a proportion of DM and PM combined, and the presence of anti-transcription intermediary factor 1 (anti-TIF1-?) autoantibodies were both significantly negatively associated with latitude (OR 0.96, 95% CI 0.95?0.98, P <?0.001; and OR 0.95, 95% CI 0.92?0.99, P =?0.004, respectively). HLA alleles significantly associated with anti-Mi-2 and anti-TIF1-? autoantibodies also were strongly negatively associated with latitude (OR 0.97, 95% CI 0.96?0.98, P <?0.001 and OR 0.98, 95% CI 0.97?0.99, P <?0.001, respectively). The frequency of five PM- or DM-associated SNPs showed a significant association with latitude (P <?0.05), and the direction of four of these associations was consistent with the latitude associations of the clinical phenotypes. Conclusions These results lend some support to the hypothesis that genetic background, in addition to UV exposure, may contribute to the distribution of DM.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Anti-Mi-2 Anti-TIF1-γ Dermatomyositis Latitude Polymyositis Ultraviolet light
Megjelenés:	Arthritis Research & Therapy. - 20 : 1 (2018), p. 1-5. -
További szerzők:	Rothwell, Simon Oldroyd, Alexander Chinoy, Hector Lamb, Janine A. Dankó Katalin (1952-2021) (belgyógyász, allergológus és klinikai immunológus) Myositis Genetics Consortium (MYOGEN)
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001-es BibID:	BIBFORM083544
035-os BibID:	(WoS)000471138100032 (Scopus)85067232111
Első szerző:	Rothwell, Simon
Cím:	Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups / Simon Rothwell, Hector Chinoy, Janine A. Lamb, Frederick W. Miller, Lisa G. Rider, Lucy R. Wedderburn, Neil J. McHugh, Andrew L. Mammen, Zoe E. Betteridge, Sarah L. Tansley, John Bowes, Jiří Vencovský, Claire T. Deakin, Katalin Dankó, Limaye Vidya, Albert Selva-O'Callaghan, Lauren M. Pachman, Ann M. Reed, Øyvind Molberg, Olivier Benveniste, Pernille R. Mathiesen, Timothy R. D. J. Radstake, Andrea Doria, Jan de Bleecker, Annette T. Lee, Michael G. Hanna, Pedro M. Machado, William E. Ollier, Peter K. Gregersen, Leonid Padyukov, Terrance P. O'Hanlon, Robert G. Cooper, Ingrid E. Lundberg, Myositis Genetics Consortium (MYOGEN)
Dátum:	2019
ISSN:	0003-4967
Megjegyzések:	OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies. METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups. RESULTS: We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9?10-5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B08:01, p=2.28?10-53?and HLA-DRB103:01, p=3.25?10-9), anti-PM/Scl (HLA-DQB102:01, p=1.47?10-26) and anti-cN1A autoantibodies (HLA-DRB103:01, p=1.40?10-11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB107:01, p=4.92?10-13) and anti-HMGCR autoantibodies (HLA-DRB111, p=5.09?10-6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47?10-64) and position 9 of HLA-B (p=7.03?10-11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies. CONCLUSIONS: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk HLA autoantibody genetics idiopathic inflammatory myopathy myositis
Megjelenés:	Annals Of The Rheumatic Diseases. - 78 : 7 (2019), p. 996-1002. -
További szerzők:	Chinoy, Hector Lamb, Janine A. Miller, Frederick W. Rider, Lisa G. Wedderburn, Lucy R. McHugh, Neil Mammen, Andrew Betteridge, Zoe Tansley, Sarah Bowes, John Vencovsky, Jiri Deakin, Claire T. Dankó Katalin (1952-2021) (belgyógyász, allergológus és klinikai immunológus) Vidya, Limaye Selva-O'Callaghan, Albert Pachman, Lauren M. Reed, Ann M. Molberg, Øyvind Benveniste, Olivier Mathiesen, Pernille R. Radstake, Timothy R. D. J. Doria, Andrea De Bleecker, Jan Lee, Annette Hanna, Michael G. Machado, Pedro M. Ollier, William E. Gregersen, Peter K. Padyukov, Leonid O'Hanlon, Terrance P. Cooper, Robert G. Lundberg, Ingrid Myositis Genetics Consortium (MYOGEN)
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001-es BibID:	BIBFORM073204
Első szerző:	Rothwell, Simon
Cím:	Immune-Array Analysis in Sporadic Inclusion Body Myositis Reveals HLA-DRB1 Amino Acid Heterogeneity Across the Myositis Spectrum / Simon Rothwell, Robert G. Cooper, Ingrid E. Lundberg, Peter K. Gregersen, Michael G. Hanna, Pedro M. Machado, Megan K. Herbert, Ger J. M. Pruijn, James B. Lilleker, Mark Roberts, John Bowes, Michael F. Seldin, Jiri Vencovsky, Katalin Danko, Vidya Limaye, Albert Selva-O'Callaghan, Hazel Platt, Øyvind Molberg, Olivier Benveniste, Timothy R. D. J. Radstake, Andrea Doria, Jan De Bleecker, Boel De Paepe, Christian Gieger, Thomas Meitinger, Juliane Winkelmann, Christopher I. Amos, William E. Ollier, Leonid Padyukov, Annette T. Lee, Janine A. Lamb, Hector Chinoy, Myositis Genetics Consortium
Dátum:	2017
ISSN:	2326-5191
Megjegyzések:	OBJECTIVE:Inclusion body myositis (IBM) is characterized by a combination of inflammatory and degenerative changes affecting muscle. While the primary cause of IBM is unknown, genetic factors may influence disease susceptibility. To determine genetic factors contributing to the etiology of IBM, we conducted the largest genetic association study of the disease to date, investigating immune-related genes using the Immunochip.METHODS:A total of 252 Caucasian patients with IBM were recruited from 11 countries through the Myositis Genetics Consortium and compared with 1,008 ethnically matched controls. Classic HLA alleles and amino acids were imputed using SNP2HLA.RESULTS:The HLA region was confirmed as the most strongly associated region in IBM (P?=?3.58 ? 10-33 ). HLA imputation identified 3 independent associations (with HLA-DRB103:01, DRB101:01, and DRB113:01), although the strongest association was with amino acid positions 26 and 11 of the HLA-DRB1 molecule. No association with anti-cytosolic 5'-nucleotidase 1A-positive status was found independent of HLA-DRB103:01. There was no association of HLA genotypes with age at onset of IBM. Three non-HLA regions reached suggestive significance, including the chromosome 3 p21.31 region, an established risk locus for autoimmune disease, where a frameshift mutation in CCR5 is thought to be the causal variant.CONCLUSION:This is the largest, most comprehensive genetic association study to date in IBM. The data confirm that HLA is the most strongly associated region and identifies novel amino acid associations that may explain the risk in this locus. These amino acid associations differentiate IBM from polymyositis and dermatomyositis and may determine properties of the peptide-binding groove, allowing it to preferentially bind autoantigenic peptides. A novel suggestive association within the chromosome 3 p21.31 region suggests a role for CCR5
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Arthritis & Rheumatology 69 : 5 (2017), p. 1090-1099. -
További szerzők:	Cooper, Robert G. Lundberg, Ingrid Gregersen, Peter K. Hanna, Michael G. Machado, Pedro M. Herbert, Megan K. Pruijn, Ger J. M. Lilleker, James B. Roberts, Mark Bowes, John Seldin, Michael F. Vencovsky, Jiri Dankó Katalin (1952-2021) (belgyógyász, allergológus és klinikai immunológus) Limaye, Vidya Selva-O'Callaghan, Albert Platt, Hazel Molberg, Øyvind Benveniste, Olivier Radstake, Timothy R. D. J. Doria, Andrea De Bleecker, Jan De Paepe, Boel Gieger, Christian Meitinger, Thomas Winkelmann, Juliane Amos, Christopher I. Ollier, William E. Padyukov, Leonid Lee, Annette Lamb, Janine A. Chinoy, Hector Myositis Genetics Consortium
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