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• W593594756 abstract "BackgroundIn recent years, a number of novel autoantibodies with defined clinical associations have been described in myositis patients. In polymyositis (PM), the major autoantibody is histidyl tRNA synthetase (Jo-1) which occurs in approximately 20-30% of patients. The remaining seven anti-tRNA-synthetases are much rarer occurring in 1-5% of patients each. Autoantibodies to the signal recognition particle (SRP) are also associated with necrotising PM and occur in 5-10% of patients. Overall, myositis specific or associated autoantibodies are only found in 50-60% of PM patients, leaving a number of patients either autoantibody negative, or with autoantibodies to unidentified targets. Here we report a further PM associated autoantibody targeting a complex of proteins in approximately 1% of PM patients with similar clinical features.MethodsSera from 250 adult polymyositis patients (based on the Bohan and Peter diagnostic criteria) recruited to the UKMyoNet or Prague cohorts were screened for autoantibodies by immunoprecipitation of 35S-labelled K562 cells. PM patients were further characterised due to the presence of the same novel precipitation pattern on SDS-PAGE and a similar clinical diagnosis. Sera from patients with this novel immunoprecipitation patterns were analysed by indirect immunofluorscence (IIF) of HEp-2 cells and immunodepletion experiments. The autoantigen complex was further characterised by immunoprecipitation and MALDI-TOF Mass Spectrometry. Sera from 273 dermatomyositis, 150 systemic sclerosis, 40 systemic lupus erythematosus patients and 50 normal controls were also screened using immunoprecipitation as controls.ResultsImmunoprecipitation of the PM patients revealed a novel pattern in three patients, with bands corresponding to approximately 160, 110, 66, 42, 41, 40, 39 and 25 kDa proteins. These patients were shown to target the identical autoantigen complex by immunodepletion experiments. Immunoprecipitation of healthy and disease controls did not find this pattern in any other group. IIF on serum from these patients displayed a fine cytoplasmic speckle. Mass Spectrometry analysis of the protein complex provisionally identified the autoantigen target as EIF3 (Eukaryotic Initiation Factor 3), a cytoplasmic complex with a role in the initiation of translation. Clinical analysis of the 3 anti-EIF3 positive patients revealed similar trends, with all patients being female, no history of malignancy or interstitial lung disease and a good response to treatment. ConclusionsUsing immunoprecipitation and a proteomic approach we report a novel autoantibody in 1% of PM patients directed against a cytoplasmic complex of proteins provisionally identified as EIF3. Whilst the numbers are low, this novel autoantibody appears to correlate with a good prognosis, with no association with cancer associated myositis or interstitial lung diseases, and a good response to treatment." @default.
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• W593594756 date "2011-04-01" @default.
• W593594756 modified "2023-09-25" @default.
• W593594756 title "Identification of autoantibodies to a novel autoantigen protein complex (EIF3) in polymyositis patients" @default.
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