Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
A Negative Anti-Nuclear Antibody Does Not Indicate Autoantibody Negativity.
Aggarwal2, Rohit, Fertig2, Noreen, Ascherman3, Dana P., Cassidy1, Elaine A., Oddis2, Chester V.
To evaluate the diagnostic utility of anti-cytoplasmic autoantibody (anti-cytAb) staining by indirect immunofluorescense (IIF) on Hep 2 substrate in anti-synthetase antibody positive (anti-synAb+) patients and to compare it with Anti-nuclear antibody (ANA) testing.
Using the Pittsburgh database of myositis and systemic sclerosis (SSc), anti-synAb+ patients were evaluated for ANA and anti-cytAb positivity. Anti-synAb+ patients included both Jo-1 and non-Jo-1 patients. SSc patients without anti-synAb were the control group. The following test characteristics of anti-cytAb and ANA were assessed in the anti-synAb+ patients: a) sensitivity [true positive (TP)/TP + false negative (FN)], b) specificity [true negative (TN)/ TN + false positive (FP)], c) positive predictive value (PPV; TP/TP + FP), d) negative predictive value (NPV; TN/TN + FN) and e) accuracy (TP + TN/ total number of patients tested). Anti-cytAb testing was done using the same method as ANA testing by IIF on Hep2 cell. Both were reported simultaneously on each patient sample. Anti-synAb status was not known before the ANA and anti-cytAb determination.
All anti-synAb+ patients [n=202; Jo-1=122 patients; non-Jo-1=80 patients] between 19852009 with available serum samples were assessed. Non-Jo-1 included: anti-PL-12, anti-PL-7, anti-EJ, anti-OJ, anti-KS. Anti-cytAb showed high sensitivity (72%), specificity (91%), NPV (91%) and accuracy, but only modest PPV (44%) for anti-synAb positivity (Table 1). Similar sensitivity results were seen for Jo-1 and non-Jo-1 (PL-12, PL-7 and KS) autoAb subgroups. In contrast, the ANA showed only modest sensitivity (50%) as well as poor specificity (0.6%), PPV (5%), NPV (10%) and accuracy (5%). Positive anti-cytoplasmic staining was significantly greater in the anti-synAb+ patients than ANA positivity (72% vs. 50%, p<0.001). Moreover, 81/99 (82%) of ANA negative patients in the anti-synAb+ cohort had positive anti-cyt staining-Ab. In contrast, the control group of SSc (n=1946) showed high positive rates for ANA (1935/1946, 99%), but very low positive rates for anti-cytAb (180/1946, 9%). Combining anti-cytAb or ANA positivity to identify anti-synAb+ patients increases the sensitivity to 90% (177/196), but specificity decreases dramatically (0.4%). Finally, the combination of anti-cytAb or Jo-1 positivity shows high sensitivity (181/196, 92%) and specificity (91%) for identification of anti-synAb+ patients.
Table 1. Anti-cytAb and ANA sensitivity, specificity, NPV, PPV, and accuracy for anti-synAb+ patients
Assessing patients for anti-cytAb staining using similar techniques to current ANA testing has excellent diagnostic utility for anti-synAb+ patients while ANA testing alone has poor test characteristics. Cytoplasmic staining should therefore be assessed and reported for patients suspected of having a rheumatic disease (RD), and a negative ANA should not be used to exclude a RD diagnosis.
To cite this abstract, please use the following information:
Aggarwal, Rohit, Fertig, Noreen, Ascherman, Dana P., Cassidy, Elaine A., Oddis, Chester V.; A Negative Anti-Nuclear Antibody Does Not Indicate Autoantibody Negativity. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :913