Background High-throughput high-sensitivity ELISAs for autoantibodies associated with CTD, such as extractable nuclear antigens (ENA), are used widely. Anti-Jo-1 (anti-histidyl-tRNA synthetase), one of this panel, is believed to confer a poor prognosis due to an association with interstitial lung disease (ILD) and myositis.
Objectives To describe: the pattern of anti-ENA positive tests; frequency of repeated requests; stability and repeatability of anti-Jo-1 tests; clinical characteristics of anti-Jo-1 +ves compared with controls; and diagnostic value of anti-Jo-1 for ILD.
Methods All anti-ENA test requests, from any hospital department, between Jan 2013 and Dec 2014 were identified. Serum samples are screened for ENA (Quanta Lite® ENA profile, Inova Diagnostics) and positive samples have specific ENA antibodies levels quantified. Data from anti-Jo-1 positive patients and controls was extracted from electronic records allowing a minimum of 12 months after first test.
Results4009 samples from 3581 patients were tested. The first sample tested, chronologically, was designated test of interest. 616 (17.2%) patients were anti-ENA screen +ve, and 40 (1.1%) anti-Jo-1 +ve (>20 AU/mL). Anti-ENA tests were done more than once for 350/3581 (9.8%) patients (428/4009 (10.7%) samples) and for 7/40 (17.5%) of anti-Jo-1 +ve patients. The median interval between 1st and 2nd requests: 124 days (IQR 233 days). The Table shows data for anti-Jo-1 patients and randomly selected ENA -ve controls. The frequency of ILD, myositis and Raynaud's was comparable. Sensitivity and specificity of Jo-1 for ILD, a key feature of “anti-synthetase syndrome”, were 50% (CI 19–81%) and 68% (CI 59–77%) respectively. Positive predictive value 12.5% (CI 4 to 27%) and negative predictive value 93.8% (CI 86–98%). Of patients with the highest anti-Jo1 titres (≥40 AU/mL, 10/40 patients, 25%): 3 had ILD, 1 myositis and 2 had a malignancy (disseminated melanoma and CML). Bland-Altman plots show that anti-Jo-1 values remained stable when patients were re-tested at another time but re-testing available stored samples from +ve patients showed important variation (Figure).
Conclusions Anti-Jo-1 is uncommon in a heterogenous hospital population and is only weakly predictive for ILD. When tested repeatedly levels remain stable over many months. Repeated testing for anti-ENA is common and potentially unnecessary. Controls over repeated requests could yield cost savings.
Disclosure of Interest None declared
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