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Research ArticleArticle

A Negative Antinuclear Antibody Does Not Indicate Autoantibody Negativity in Myositis: Role of Anticytoplasmic Antibody as a Screening Test for Antisynthetase Syndrome

Rohit Aggarwal, Namrata Dhillon, Noreen Fertig, Diane Koontz, Zengbiao Qi and Chester V. Oddis
The Journal of Rheumatology December 2016, jrheum.160618; DOI: https://doi.org/10.3899/jrheum.160618
Rohit Aggarwal
From the Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. R. Aggarwal, MD, MS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Dhillon, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Fertig, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; D. Koontz, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; Z. Qi, PhD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; C.V. Oddis, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine. Address correspondence to Dr. R. Aggarwal, Associate Professor of Medicine, University of Pittsburgh, 3500 Fifth Ave., Suite 2B, Falk Medical Building, Arthritis and Autoimmunity Center, Pittsburgh, Pennsylvania 15213, USA. E-mail: aggarwalr{at}upmc.edu. Accepted for publication October 19, 2016.
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Namrata Dhillon
From the Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. R. Aggarwal, MD, MS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Dhillon, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Fertig, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; D. Koontz, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; Z. Qi, PhD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; C.V. Oddis, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine. Address correspondence to Dr. R. Aggarwal, Associate Professor of Medicine, University of Pittsburgh, 3500 Fifth Ave., Suite 2B, Falk Medical Building, Arthritis and Autoimmunity Center, Pittsburgh, Pennsylvania 15213, USA. E-mail: aggarwalr{at}upmc.edu. Accepted for publication October 19, 2016.
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Noreen Fertig
From the Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. R. Aggarwal, MD, MS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Dhillon, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Fertig, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; D. Koontz, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; Z. Qi, PhD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; C.V. Oddis, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine. Address correspondence to Dr. R. Aggarwal, Associate Professor of Medicine, University of Pittsburgh, 3500 Fifth Ave., Suite 2B, Falk Medical Building, Arthritis and Autoimmunity Center, Pittsburgh, Pennsylvania 15213, USA. E-mail: aggarwalr{at}upmc.edu. Accepted for publication October 19, 2016.
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Diane Koontz
From the Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. R. Aggarwal, MD, MS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Dhillon, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Fertig, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; D. Koontz, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; Z. Qi, PhD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; C.V. Oddis, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine. Address correspondence to Dr. R. Aggarwal, Associate Professor of Medicine, University of Pittsburgh, 3500 Fifth Ave., Suite 2B, Falk Medical Building, Arthritis and Autoimmunity Center, Pittsburgh, Pennsylvania 15213, USA. E-mail: aggarwalr{at}upmc.edu. Accepted for publication October 19, 2016.
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Zengbiao Qi
From the Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. R. Aggarwal, MD, MS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Dhillon, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Fertig, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; D. Koontz, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; Z. Qi, PhD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; C.V. Oddis, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine. Address correspondence to Dr. R. Aggarwal, Associate Professor of Medicine, University of Pittsburgh, 3500 Fifth Ave., Suite 2B, Falk Medical Building, Arthritis and Autoimmunity Center, Pittsburgh, Pennsylvania 15213, USA. E-mail: aggarwalr{at}upmc.edu. Accepted for publication October 19, 2016.
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Chester V. Oddis
From the Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. R. Aggarwal, MD, MS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Dhillon, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; N. Fertig, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; D. Koontz, BS, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; Z. Qi, PhD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; C.V. Oddis, MD, Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine. Address correspondence to Dr. R. Aggarwal, Associate Professor of Medicine, University of Pittsburgh, 3500 Fifth Ave., Suite 2B, Falk Medical Building, Arthritis and Autoimmunity Center, Pittsburgh, Pennsylvania 15213, USA. E-mail: aggarwalr{at}upmc.edu. Accepted for publication October 19, 2016.
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Abstract

Objective To evaluate the utility of anticytoplasmic autoantibody (anti-CytAb) in antisynthetase antibody–positive (anti-SynAb+) patients.

Methods Anti-SynAb+ patients were evaluated for antinuclear antibody (ANA) and anti-CytAb [cytoplasmic staining on indirect immunofluorescence (IIF)] positivity. Anti-SynAb+ patients included those possessing anti-Jo1 and other antisynthetase autoantibodies. Control groups included scleroderma, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, and healthy subjects. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy of anti-CytAb, and ANA were assessed. Anti-CytAb and ANA testing was done by IIF on human epithelial cell line 2, both reported on each serum sample without knowledge of the clinical diagnosis or final anti-SynAb results.

Results Anti-SynAb+ patients (n = 202; Jo1, n = 122; non-Jo1, n = 80) between 1985–2013 with available serum samples were assessed. Anti-CytAb showed high sensitivity (72%), specificity (89%), NPV (95%), and accuracy (86%), but only modest PPV (54%) for anti-SynAb positivity. In contrast, ANA showed only modest sensitivity (50%) and poor specificity (6%), PPV (9%), NPV (41%), and accuracy (12%). Positive anti-CytAb was significantly greater in the anti-SynAb+ patients than ANA positivity (72% vs 50%, p < 0.001), and 81/99 (82%) ANA-negative patients in the anti-SynAb+ cohort had positive anti-CytAb. In contrast, the control groups showed high rates for ANA positivity (93.5%), but very low rates for anti-CytAb positivity (11.5%). Combining anti-CytAb or Jo1 positivity showed high sensitivity (92%) and specificity (89%) for identification of anti-SynAb+ patients.

Conclusion Assessing patients for anti-CytAb serves as an excellent screen for anti-SynAb+ patients using simple IIF. Cytoplasmic staining should be assessed and reported for patients suspected of having antisynthetase syndrome and a negative ANA should not be used to exclude this diagnosis.

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The Journal of Rheumatology: 53 (8)
The Journal of Rheumatology
Vol. 53, Issue 8
1 Aug 2026
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A Negative Antinuclear Antibody Does Not Indicate Autoantibody Negativity in Myositis: Role of Anticytoplasmic Antibody as a Screening Test for Antisynthetase Syndrome
Rohit Aggarwal, Namrata Dhillon, Noreen Fertig, Diane Koontz, Zengbiao Qi, Chester V. Oddis
The Journal of Rheumatology Dec 2016, jrheum.160618; DOI: 10.3899/jrheum.160618

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A Negative Antinuclear Antibody Does Not Indicate Autoantibody Negativity in Myositis: Role of Anticytoplasmic Antibody as a Screening Test for Antisynthetase Syndrome
Rohit Aggarwal, Namrata Dhillon, Noreen Fertig, Diane Koontz, Zengbiao Qi, Chester V. Oddis
The Journal of Rheumatology Dec 2016, jrheum.160618; DOI: 10.3899/jrheum.160618
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