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Reasons For Requesting the Test in Antinuclear Antibody-Positive Patients and Final Diagnosis of Patients

Year 2023, Volume: 17 Issue: 5, 347 - 353, 25.09.2023
https://doi.org/10.12956/tchd.1266045

Abstract

Background: The aim of this study was to determine the reasons for the request for antinuclear antibody (ANA) in ANA-positive patients and to determine the final diagnosis of these patients and whether they developed a rheumatologic disease.

Method: In this retrospective study, the files of 559 patients with positive ANA were reviewed. Demographic, laboratory and clinical characteristics of the patients were noted. At the end of follow-up, the final diagnosis was recorded.

Results: The study included 346 patients. 233 of the patients were female, and 113 were male. The mean age at the time of ANA positivity was 9.4  4.7 years, and the mean follow-up period was 19  5.7 months. The most common symptom was myalgia/arthralgia (21.7%). Other common reasons were urticaria, abdominal pain, thrombocytopenia, and proteinuria. Extractable nuclear antigens (ENA) panel results were negative in 170 patients (49.1%). In the ENA panel, dense fine speckled antigen 70 antibodies were most frequently positive in 135 patients (39.2%). At the end of follow-up, 234 patients had no disease. One hundred and one patients were diagnosed with non-rheumatologic diseases, and 11 patients were diagnosed with rheumatologic diseases. Eleven patients with rheumatologic diseases were girls. Rash was the most common symptom in patients with rheumatologic diseases. The positive predictive value of ANA positivity for rheumatologic disease was 3.2% and 1.7% for systemic lupus erythematosus.

Conclusions: Due to the low positive predictive value of ANA testing, patients at risk for autoimmune diseases should be identified and carefully evaluated before ANA is requested.

References

  • Irure-Ventura J, López-Hoyos M. The Past, Present, and Future in Antinuclear Antibodies (ANA). Diagnostics 2022;12:647.
  • Bossuyt X, De Langhe E, Borghi MO, Meroni PL. Understanding and interpreting antinuclear antibody tests in systemic rheumatic diseases. Nat Rev Rheumatol 2020;16:715-26.
  • Conrad K, Shoenfeld Y, Fritzler MJ. Precision health: A pragmatic approach to understanding and addressing key factors in autoimmune diseases. Autoimmun Rev 2020;19:102508. 
  • Xiao Y, Lin Y, Zhang Y, Wang J, Zeng Y. Factors associated with the antinuclear antibody (ANA) titer of systemic autoimmune rheumatic diseases in ANA-positive patients after treatment: a retrospective study. Clin Exp Med 2022;22:439-46.
  • Mahler M, Andrade LE, Casiano CA, Malyavantham K, Fritzler MJ. Anti-DFS70 antibodies: an update on our current understanding and their clinical usefulness. Expert Rev Clin Immunol 2019;15:241-50.
  • Carbone T, Pafundi V, Tramontano G, Gilio M, Padula MC, Padula AA, et al. Prevalence and serological profile of anti-DFS70 positive subjects from a routine ANA cohort. Sci Rep 2019;9:2177.
  • Hayashi N, Uto K, Imanishi A, Sugiyama D, Morinobu A, Saegusa J. Prevalence of anti-dense fine speckled 70 antibodies in healthy individuals and patients with antinuclear antibody-associated autoimmune rheumatic diseases in Japan. Medicine (Baltimore) 2021;100:e24556. 
  • Sur LM, Floca E, Sur DG, Colceriu MC, Samasca G, Sur G. Antinuclear Antibodies: Marker of Diagnosis and Evolution in Autoimmune Diseases. Lab med 2018;49:e62–e73.
  • Davis LA, Goldstein B, Tran V, Keniston A, Yazdany J, Hirsh J, et al. Applying Choosing Wisely: Antinuclear Antibody (ANA) and Sub-Serology Testing in a Safety Net Hospital System. Open Rheumatol J 2015;9:82-7.
  • Racoubian E, Zubaid RM, Shareef MA, Almawi WY. Prevalence of antinuclear antibodies in healthy Lebanese subjects, 2008-2015: a cross-sectional study involving 10,814 subjects. Rheumatol Int 2016;36:1231-6.
  • Haslak F, Yildiz M, Altun I, Yilmaz G, Adrovic A, Sahin S, et al. Anti-nuclear antibody testing in children: How much is really necessary?. Pediatr Int 2021;63:1020-5.
  • Kang SH, Seo YI, Lee MH, Kim HA. Diagnostic Value of Anti-Nuclear Antibodies: Results From Korean University-Affiliated Hospitals. J Korean Med Sci 2022;37:e159 . Wener MH, Fink SL, Morishima C, Chaudhary A, Hutchinson K. Anti-Nuclear Antibody Quantitation: Calibration and Harmonization Adjustment via Population Interrogation. J Appl Lab Med 2022;7:46-56.
  • Karakeçe E, Atasoy AR, Çakmak G, Tekeoglu I, Harman H, Çiftci IH. Bir üniversite hastanesinde antinükleer antikor pozitiflikleri. Turk J Immunol 2014;2:5-8.
  • van Beers JJBC, Koek GH, Damoiseaux JGMC. The Role of Autoantibodies in the Diagnosis of Autoimmune Liver Disease: Lessons Learned from Clinical Practice. J Appl Lab Med 2022;7:259-67.
  • Grygiel-Górniak B, Rogacka N, Puszczewicz M. Antinuclear antibodies in healthy people and non-rheumatic diseases - diagnostic and clinical implications. Reumatologia 2018;56:243-8.
  • Abeles AM, Abeles M. The clinical utility of a positive antinuclear antibody test result. Am J Med 2013;126:342-8.
  • Batu ED, Sönmez HE, Bilginer Y. Characteristics of Patients Referred to the Pediatric Rheumatology Polyclinic with Anti-Nuclear Antibody (ANA) Positivity. Turkish J Pediatr Dis 2018;13:13-8.
  • Pashnina IA, Krivolapova IM, Fedotkina TV, Ryabkova VA, Chereahneva MV, Churilov LP, et al. Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease. Antibodies (Basel) 2021;10:9. https://anapatterns.org (Date of access: 10.02.2023
  • Didier K, Bolko L, Giusti D, et al. Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians?. Front Immunol 2018;9:541.
  • Yeo AL, Leech M, Ojaimi S, Morand E. Utility of repeat extractable nuclear antigen antibody testing: a retrospective audit. Rheumatology (Oxford) 2023;62:1248-53.

Antinükleer Antikor Pozitif Hastalarda Test İsteme Nedenleri ve Hastaların Nihai Tanıları

Year 2023, Volume: 17 Issue: 5, 347 - 353, 25.09.2023
https://doi.org/10.12956/tchd.1266045

Abstract

Amaç: Bu çalışmanın amacı ANA-pozitif hastalarda antinükleer antikor (ANA) istenmesinin nedenlerini belirlemek ve bu hastaların son tanılarını ve romatolojik bir hastalık geliştirip geliştirmediklerini saptamaktır.

Yöntem: Bu çalışmada ANA pozitif 559 hastanın dosyaları geriye dönük incelendi. Hastaların demografik, laboratuvar ve klinik özellikleri kaydedildi. Takip sonunda son tanıları kaydedildi.

Bulgular: Çalışmaya 346 hasta dahil edildi. Hastaların 233'ü kadın, 113'ü erkekti. ANA pozitifliği saptandığında, ortalama yaş 9,4  4,7 yıl ve ortalama takip süresi 19  5,7 aydı. En sık görülen semptom miyalji/artraljiydi (%21,7). Diğer yaygın nedenler ürtiker, karın ağrısı, trombositopeni ve proteinüri idi. Ekstrakte edilebilir nükleer antijenler (ENA) panel sonuçları 170 hastada (%49,1) negatifti. ENA panelinde en sık 135 hastada (%39,2) yoğun ince benekli antijen 70 antikorları pozitif bulunmuştur. Takip sonunda 234 hastada hastalık yoktu. Yüz bir hastaya romatolojik olmayan hastalık, 11 hastaya ise romatolojik hastalık tanısı konuldu. Romatolojik hastalığı olan 11 hasta kızdı. Romatolojik hastalığı olan hastalarda döküntü en sık görülen semptomdu. ANA pozitifliğinin romatolojik hastalıklar için pozitif prediktif değeri %3,2 ve sistemik lupus eritematozus için %1,7 idi.

Sonuç: ANA testinin pozitif prediktif değerinin düşük olması nedeniyle, otoimmün hastalıklar açısından risk altında olan hastalar ANA istenmeden önce belirlenmeli ve dikkatle değerlendirilmelidir.

References

  • Irure-Ventura J, López-Hoyos M. The Past, Present, and Future in Antinuclear Antibodies (ANA). Diagnostics 2022;12:647.
  • Bossuyt X, De Langhe E, Borghi MO, Meroni PL. Understanding and interpreting antinuclear antibody tests in systemic rheumatic diseases. Nat Rev Rheumatol 2020;16:715-26.
  • Conrad K, Shoenfeld Y, Fritzler MJ. Precision health: A pragmatic approach to understanding and addressing key factors in autoimmune diseases. Autoimmun Rev 2020;19:102508. 
  • Xiao Y, Lin Y, Zhang Y, Wang J, Zeng Y. Factors associated with the antinuclear antibody (ANA) titer of systemic autoimmune rheumatic diseases in ANA-positive patients after treatment: a retrospective study. Clin Exp Med 2022;22:439-46.
  • Mahler M, Andrade LE, Casiano CA, Malyavantham K, Fritzler MJ. Anti-DFS70 antibodies: an update on our current understanding and their clinical usefulness. Expert Rev Clin Immunol 2019;15:241-50.
  • Carbone T, Pafundi V, Tramontano G, Gilio M, Padula MC, Padula AA, et al. Prevalence and serological profile of anti-DFS70 positive subjects from a routine ANA cohort. Sci Rep 2019;9:2177.
  • Hayashi N, Uto K, Imanishi A, Sugiyama D, Morinobu A, Saegusa J. Prevalence of anti-dense fine speckled 70 antibodies in healthy individuals and patients with antinuclear antibody-associated autoimmune rheumatic diseases in Japan. Medicine (Baltimore) 2021;100:e24556. 
  • Sur LM, Floca E, Sur DG, Colceriu MC, Samasca G, Sur G. Antinuclear Antibodies: Marker of Diagnosis and Evolution in Autoimmune Diseases. Lab med 2018;49:e62–e73.
  • Davis LA, Goldstein B, Tran V, Keniston A, Yazdany J, Hirsh J, et al. Applying Choosing Wisely: Antinuclear Antibody (ANA) and Sub-Serology Testing in a Safety Net Hospital System. Open Rheumatol J 2015;9:82-7.
  • Racoubian E, Zubaid RM, Shareef MA, Almawi WY. Prevalence of antinuclear antibodies in healthy Lebanese subjects, 2008-2015: a cross-sectional study involving 10,814 subjects. Rheumatol Int 2016;36:1231-6.
  • Haslak F, Yildiz M, Altun I, Yilmaz G, Adrovic A, Sahin S, et al. Anti-nuclear antibody testing in children: How much is really necessary?. Pediatr Int 2021;63:1020-5.
  • Kang SH, Seo YI, Lee MH, Kim HA. Diagnostic Value of Anti-Nuclear Antibodies: Results From Korean University-Affiliated Hospitals. J Korean Med Sci 2022;37:e159 . Wener MH, Fink SL, Morishima C, Chaudhary A, Hutchinson K. Anti-Nuclear Antibody Quantitation: Calibration and Harmonization Adjustment via Population Interrogation. J Appl Lab Med 2022;7:46-56.
  • Karakeçe E, Atasoy AR, Çakmak G, Tekeoglu I, Harman H, Çiftci IH. Bir üniversite hastanesinde antinükleer antikor pozitiflikleri. Turk J Immunol 2014;2:5-8.
  • van Beers JJBC, Koek GH, Damoiseaux JGMC. The Role of Autoantibodies in the Diagnosis of Autoimmune Liver Disease: Lessons Learned from Clinical Practice. J Appl Lab Med 2022;7:259-67.
  • Grygiel-Górniak B, Rogacka N, Puszczewicz M. Antinuclear antibodies in healthy people and non-rheumatic diseases - diagnostic and clinical implications. Reumatologia 2018;56:243-8.
  • Abeles AM, Abeles M. The clinical utility of a positive antinuclear antibody test result. Am J Med 2013;126:342-8.
  • Batu ED, Sönmez HE, Bilginer Y. Characteristics of Patients Referred to the Pediatric Rheumatology Polyclinic with Anti-Nuclear Antibody (ANA) Positivity. Turkish J Pediatr Dis 2018;13:13-8.
  • Pashnina IA, Krivolapova IM, Fedotkina TV, Ryabkova VA, Chereahneva MV, Churilov LP, et al. Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease. Antibodies (Basel) 2021;10:9. https://anapatterns.org (Date of access: 10.02.2023
  • Didier K, Bolko L, Giusti D, et al. Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians?. Front Immunol 2018;9:541.
  • Yeo AL, Leech M, Ojaimi S, Morand E. Utility of repeat extractable nuclear antigen antibody testing: a retrospective audit. Rheumatology (Oxford) 2023;62:1248-53.
There are 20 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section ORIGINAL ARTICLES
Authors

Nimet Öner 0000-0003-0403-151X

Elif Çelikel 0000-0003-0129-4410

Zahide Ekici Tekin 0000-0002-5446-667X

Vildan Güngörer 0000-0002-9838-2603

Serkan Coşkun 0000-0003-2568-9329

Melike Mehveş Kaplan 0000-0002-8012-2774

Cüneyt Karagöl 0000-0002-2987-1980

Nilüfer Tekgöz 0000-0002-2235-4489

Müge Sezer 0000-0002-9254-9935

Merve Cansu Polat 0000-0003-3279-8435

Banu Acar 0000-0002-1808-3655

Early Pub Date June 14, 2023
Publication Date September 25, 2023
Submission Date March 16, 2023
Published in Issue Year 2023 Volume: 17 Issue: 5

Cite

Vancouver Öner N, Çelikel E, Ekici Tekin Z, Güngörer V, Coşkun S, Kaplan MM, Karagöl C, Tekgöz N, Sezer M, Polat MC, Acar B. Reasons For Requesting the Test in Antinuclear Antibody-Positive Patients and Final Diagnosis of Patients. Türkiye Çocuk Hast Derg. 2023;17(5):347-53.


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