Cardiac involvement in myositis



THE 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

H. Chinoy1, S. Adimulam1, F. Marriage2, P. New1, M. Vincze3, E. Zilahi3, A. Kapitány3, A. Gyetvai3, L. Ekholm4, P. Novota5, M. Remakova5, P. Charles6, N.J. McHugh7, L. Padyukov4, L. Alfredsson8, J. Vencovsky5, I. E. Lundberg4, K. Danko3, W. E. Ollier2, R. G. Cooper1,2

1Rheumatic Diseases Centre, Manchester Academic Health Science Centre, The University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK;

2Centre for Integrated Genomic Medical Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK

3Division of Clinical Immunology, University of Debrecen, Debrecen, Hungary; 4Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden;

5Institute of Rheumatology, Charles University, Prague, Czech Republic;

6Kennedy Institute of Rheumatology, Imperial College, London, UK

7Royal National Hospital for Rheumatic Diseases, Bath, UK

8Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Address for reprints and correspondence:

Professor Robert G Cooper

The University of Manchester Rheumatic Diseases Centre,

Salford Royal NHS Foundation Trust,

Eccles Old Road, Salford,

M6 8HD.

Tel/fax: +44-(0)161-206-1483

Email: robert.g.cooper@manchester.ac.uk

Key words: Myositis, antibodies, smoking, gene-environment interactions, HLA

Word count:

2,151

Abstract

Objectives: HLA-DRB1*03 is strongly associated with anti-Jo-1 positive IIM and there is now increasing evidence that Jo-1 antigen is preferentially expressed in lung tissue. The aim was to examine whether smoking was associated with development of anti-Jo-1 antibodies in HLA-DRB1*03 positive IIM.

Methods: IIM cases were selected with concurrent information regarding HLA-DRB1 status, smoking history and anti-Jo-1 antibody status. DNA was genotyped at DRB1 using a commercial sequence-specific oligonucleotide kit. Anti-Jo-1 antibody status was established using a line blot assay or immunoprecipitation.

Results: 557 Caucasian IIM patients were recruited from Hungary (181), UK (99), Sweden (94) and Czech Republic (183). Smoking frequency was increased in anti-Jo-1 positive IIM cases, and reached statistical significance in Hungarian IIM (45% Jo-1+ vs 17% Jo-1-, odds ratio [OR] 3.94, 95% confidence interval 1.53-9.89, p ................
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