ABSTRACT
A 58-year-old lady with a previous diagnosis of rheumatoid arthritis (RA) was referred to Rheumatology to manage her joint pains. On evaluation, it was noted that the lady did not have any signs of synovial inflammation. The patient had a negative anti-cyclic citrullinated peptide (anti-CCP) (<0.5) and negative rheumatoid factor (RF) (<10) together with high ferritin (1,507 µg/L) which led to consideration of hereditary hemochromatosis (HH) rather than RA. She was then referred to Hematology for regular venesection which settled her symptoms. This case report highlights the importance of considering HH as a differential diagnosis in patients with chronic arthritis particularly if there are no clinical signs and negative tests for RA. More retrospective studies will be needed to quantify how many cases of hemochromatosis arthropathy have been mistakenly diagnosed as RA.
ABSTRACT
OBJECTIVES: To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. METHODS: Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren's syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. RESULTS: IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. CONCLUSION: We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.
