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  • 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

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Clinical and epidemiological research
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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
  1. H Chinoy1,
  2. S Adimulam1,
  3. F Marriage2,
  4. P New1,
  5. M Vincze3,
  6. E Zilahi3,
  7. A Kapitány3,
  8. A Gyetvai3,
  9. L Ekholm4,
  10. P Novota5,
  11. M Remakova5,
  12. P Charles6,
  13. N J McHugh7,
  14. L Padyukov4,
  15. L Alfredsson8,
  16. J Vencovsky5,
  17. I E Lundberg4,
  18. K Danko3,
  19. W E Ollier2,
  20. R G Cooper1,2
  1. 1Rheumatic Diseases Centre, Manchester Academic Health Science Centre, The University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK
  2. 2Centre for Integrated Genomic Medical Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
  3. 3Division of Clinical Immunology, University of Debrecen, Debrecen, Hungary
  4. 4Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
  5. 5Institute of Rheumatology, Charles University, Prague, Czech Republic
  6. 6Kennedy Institute of Rheumatology, Imperial College, London, UK
  7. 7Royal National Hospital for Rheumatic Diseases, Bath, UK
  8. 8Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
  1. Correspondence to Robert G Cooper, Rheumatic Diseases Centre, Manchester Academic Health Science Centre, The University of Manchester, Salford Royal NHS Foundation Trust, Eccles Old Road, Salford M6 8HD, UK; robert.g.cooper{at}manchester.ac.uk

Abstract

Objectives HLA-DRB1*03 is strongly associated with anti-Jo-1-positive idiopathic inflammatory myopathies (IIM) and there is now increasing evidence that Jo-1 antigen is preferentially expressed in lung tissue. This study examined whether smoking was associated with the 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-positive vs 17% Jo-1-negative, OR 3.94, 95% CI 1.53 to 9.89, p<0.0001). A strong association between HLA-DRB1*03 and anti-Jo-1 status was observed across all four cohorts (DRB1*03 frequency: 74% Jo-1-positive vs 35% Jo-1-negative, OR 5.55, 95% CI 3.42 to 9.14, p<0.0001). The frequency of HLA-DRB1*03 was increased in smokers. The frequency of anti-Jo-1 was increased in DRB1*03-positive smokers vs DRB1*03-negative non-smokers (42% vs 8%, OR 7.75, 95% CI 4.21 to 14.28, p<0.0001) and DRB1*03-positive non-smokers (42% vs 31%, p=0.08). In DRB1*03-negative patients, anti-Jo-1 status between smokers and non-smokers was not significantly different. No significant interaction was noted between smoking and DRB1*03 status using anti-Jo-1 as the outcome measure.

Conclusion Smoking appears to be associated with an increased risk of possession of anti-Jo-1 in HLA-DRB1*03-positive IIM cases. The authors hypothesise that an interaction between HLA-DRB1*03 and smoking may prime the development of anti-Jo-1 antibodies.

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl

https://doi.org/10.1136/annrheumdis-2011-200182

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    Footnotes

    • Funding This study received funding from the Myositis Support Group (UK). JV receives institutional support MSM 0021620812 from the Ministry of Education, Youth and Sports in the Czech Republic. The Swedish study has received funding from the Swedish Research Council, the Swedish Rheumatism Association, King Gustaf V 80 Year Foundation, Funds at the Karolinska Institutet, the European Union Sixth Framework Programme (project AutoCure; LSH-018661), and through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet. The Hungarian study was supported by a ETT 2 FAE 1 KCOO90819 grant.

    • Ethics approval Ethics approval was received from the local research ethics committees.

    • Patient consent Obtained.

    • Competing interests None.

    • Provenance and peer review Not commissioned; externally peer reviewed.