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.

Children's Hospital Pittsburg, Pittsburgh, PA
University of Pittsburgh, Pittsburgh, PA
University of Pittsburgh, Pittsburgh, PA

Purpose:

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.

Methods:

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.

Results:

All anti-synAb+ patients [n=202; Jo-1=122 patients; non-Jo-1=80 patients] between 1985–2009 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

Test StatisticANAAnti-cytAbp value
Sensitivity
  All anti-synAb patients100/199 (50%)142/196 (72%)p<0.001
    All Jo-162/119 (52%)77/116 (66%)p=0.026
    All non-Jo-138/80 (48%)65/80 (81%)p<0.001
      PL-1217/35 (49%)30/35 (86%)p<0.001
      PL-713/25 (52%)23/25 (92%)p<0.001
      EJ3/9 (33%)4/9 (44%)NS
      KS2/6 (33%)6/6 (100%)p=0.013
      OJ3/5 (60%)2/5 (40%)NS
Specificity*0.60%91% 
NPV*10%91% 
PPV*5%44% 
Accuracy*5%89% 
*All anti-synAb group  NS = not significant

Conclusions:

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
DOI: 10.1002/art.28681

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