Clinical and Autoantibody Associations in Myositis Patients with Anti p155/140kDa Autoantibodies - A Multicenter European Study

Background/Purpose: Malignancy is common among patients withdermatomyositis (DM). A novel myositis specific autoantibody (autoAb)directed against a 155/140 kDa (p155/140) protein has been reported inassociation with cancer associated DM. This study investigated anti-p155/140 antibodies in patients with idiopathic inflammatory myopathies from3 European centers and the association with malignancy types and withthe presence of other concurrent autoantibodies.Methods: A multi-center cross sectional study of adult patients withIIM was performed as a part of ongoing collaboration within theEuMyoNet project. All patients fulfilled probable/definite criteria for IIMdiagnosis according to the Bohan & Peter criteria. Six hundred and fortyseven sera were tested for presence of various myositis specific andmyositis associated autoAbs by immunoprecipitation using 35S methioninelabeled extracts from K562 leukemia cell line in a single facility(Bath, UK). Clinical data regarding IIM and malignancies were collectedby treating physicians at the 3 participating sites (UK, S, CZ). Cancerassociated myositis (CAM) was defined as cancer occurring in IIMpatients within 3 years of disease onset.Results: 40 patients (6.2%) (37 DM, 2 polymyositis and 1 withIIM/CTD▫overlap syndrome) tested positive for p155/140. Patients werepredominantly Caucasian (39) and mostly women (32/40). 17/40 p155/140 positive patients (all DM) developed cancer (6 breast, 3 ovarian, 2bladder, 2 lymphatic tissue, 1 each in esophagus, gallbladder, uterus andunknown primary localization) within 3 years of IIM onset (4 prior, 8 afterand 5 concurrent with IIM). In addition one patient had a history of coloncancer 10 years prior to first IIM symptoms. The subgroup of p155/140positive CAM patients were compared to 16 p155/140 negative CAMpatients (4PM, 12DM) from 2 participating sites (S, CZ). There was nodifference in mean age at the onset of IIM (56.8_9.8 and 54.9_10.8years, p_0.6), diagnosis of cancer (57.1_9.7 and 56.1_10.6 years;p_0.78) or sex (76% vs. 73% women) between p155/140 positive andnegative groups. The type of malignancies did not differ between the twocancer groups.Seventy-five percent of the p155/140 negative CAM patients had anothermyositis specific or associated autoAb (SAE 3x, Mi-2 2x, Jo-1 2x, p140 2x,SRP 1x, U1 RNP 1x, Ro 2x) whereas only 17.5 % of the p155/140 hadanother autoantibody (Ro 4x, U1RNP 2x, KS 1x, SRP 1x).Conclusion: Prevalence of CAM in our p155/140 cohort (43%) wassimilar to that reported previously. Presence of the p155/140 autoantibody isnot restricted to DM patients only, but the increased risk of cancer associatedwith p155/140 seems to be confined to the DM population. We were not ableto identify any difference in terms of age of IIM or clinical presentationsbetween p155/140 positive and negative CAM patients. In addition thep155/140 autoAb is not exclusive as some patients may have other, evenmyositis specific autoAb, at the same time.Acknowledgement: Supported by MSM 0021620812 from Ministry ofEducation, Youth and Sports in the Czech Republic and by the EuropeanScience Foundation - EUMYONET project.