TY - CONF
T1 - The Interaction Of HLA-DRB1*03 And Smoking For The Development Of Anti-Jo-1 Antibodies In Adult Idiopathic Inflammatory Myopathies: A European-Wide Study
AU - Chinoy, H.
AU - Adimulam, S.
AU - Vincze, M.
AU - Gyetvai, A.
AU - Ekholm, L.
AU - Vencovsky, J.
AU - Lundberg, I.E.
AU - Danko, K.
AU - Ollier, WER
AU - Cooper, R.G.
PY - 2010
Y1 - 2010
N2 - Background: The aetiology of IIM is thought to result from the interaction of environmental risk factors in geneticallysusceptible individuals. HLA-DRB1*03 is strongly associated with anti-histidyl-tRNA synthetase (Jo-1) positive IIM. Inrheumatoid arthritis, an interaction between smoking and the shared epitope is thought to prime development of anti-CCPantibodies. A granzyme B-cleavable form of Jo-1 is preferentially expressed in normal alveolar epithelium1. In a UK IIMcohort, we have demonstrated that smoking appears to be associated with an increased risk for the development of anti-Jo-1 antibodies in HLA-DRB1*03 positive IIM cases2.Objectives: To replicate the finding, that smoking is associated with increased risk of development of anti-Jo-1antibodies in HLA-DRB1*03 positive IIM, in independent European cohorts.Methods: Confirmed probable/definite IIM cases3 were selected with concurrent information about HLA-DRB1, smokingand anti-Jo-1 status. DNA was genotyped at DRB1 using a commercial sequence specific oligonucleotide kit at eachcentre. Anti-Jo-1 antibody status was established using standard methodology. Smoking status was defined according tothe following question: “Have you ever smoked as much as one cigarette a day for as long as a year?”.Results: 431 Caucasian IIM patients were recruited from the following countries: Hungary (181), UK (99), Sweden (94),Czech (57); females 64%. Sub-group status was as follows: polymyositis, n=220; dermatomyositis, n=137;myositis/overlap, n=70; females 64%, median age of disease onset 47+/-14.2 years. 161 (37%) patients admitted tohaving ever smoked. The frequency of smoking was significantly increased in anti-Jo-1 positive cases (smokingfrequency: 49% Jo-1 + vs 35% Jo-1 -, odds ratio [OR] 1.8, 1.1-3.0, p=0.01). HLA-DRB1*03 was significantly associatedwith anti-Jo-1 status (DRB1*03 frequency: 74% Jo-1 + vs 35% Jo-1 -, OR 5.4, 3.1-9.8, p=8x10-11). The frequency ofDRB1*03 was increased in smokers (DRB1*03 frequency: 54% smokers vs 36% non-smokers, OR 2.1, 1.4-3.2,p=0.0002). The frequency of anti-Jo-1 was increased in DRB1*03+ smokers vs DRB1*03- non-smokers (Table 1,p
AB - Background: The aetiology of IIM is thought to result from the interaction of environmental risk factors in geneticallysusceptible individuals. HLA-DRB1*03 is strongly associated with anti-histidyl-tRNA synthetase (Jo-1) positive IIM. Inrheumatoid arthritis, an interaction between smoking and the shared epitope is thought to prime development of anti-CCPantibodies. A granzyme B-cleavable form of Jo-1 is preferentially expressed in normal alveolar epithelium1. In a UK IIMcohort, we have demonstrated that smoking appears to be associated with an increased risk for the development of anti-Jo-1 antibodies in HLA-DRB1*03 positive IIM cases2.Objectives: To replicate the finding, that smoking is associated with increased risk of development of anti-Jo-1antibodies in HLA-DRB1*03 positive IIM, in independent European cohorts.Methods: Confirmed probable/definite IIM cases3 were selected with concurrent information about HLA-DRB1, smokingand anti-Jo-1 status. DNA was genotyped at DRB1 using a commercial sequence specific oligonucleotide kit at eachcentre. Anti-Jo-1 antibody status was established using standard methodology. Smoking status was defined according tothe following question: “Have you ever smoked as much as one cigarette a day for as long as a year?”.Results: 431 Caucasian IIM patients were recruited from the following countries: Hungary (181), UK (99), Sweden (94),Czech (57); females 64%. Sub-group status was as follows: polymyositis, n=220; dermatomyositis, n=137;myositis/overlap, n=70; females 64%, median age of disease onset 47+/-14.2 years. 161 (37%) patients admitted tohaving ever smoked. The frequency of smoking was significantly increased in anti-Jo-1 positive cases (smokingfrequency: 49% Jo-1 + vs 35% Jo-1 -, odds ratio [OR] 1.8, 1.1-3.0, p=0.01). HLA-DRB1*03 was significantly associatedwith anti-Jo-1 status (DRB1*03 frequency: 74% Jo-1 + vs 35% Jo-1 -, OR 5.4, 3.1-9.8, p=8x10-11). The frequency ofDRB1*03 was increased in smokers (DRB1*03 frequency: 54% smokers vs 36% non-smokers, OR 2.1, 1.4-3.2,p=0.0002). The frequency of anti-Jo-1 was increased in DRB1*03+ smokers vs DRB1*03- non-smokers (Table 1,p
M3 - Poster
SP - 69(Suppl3):246
T2 - EULAR
Y2 - 1 January 1824
ER -