Concepta Otomatik ANA Tespit Sisteminin Rutin Klinik Örneklerde Performans Değerlendirmesi

Year 2025, Issue: Early Access

Mehmet Akif Durmuş , Ayşe Nur Ceylan , Kübra Evren

https://doi.org/10.18678/dtfd.1607920

Abstract

Amaç: Anti-nükleer antikorların (ANA) tanısında HEp-2 hücrelerinin kullanıldığı indirekt immünofloresans (IIF) testi, yüksek duyarlılığı nedeniyle standart yöntemdir. Son yıllarda, IIF yöntemi ile ANA tespitinde standardizasyonu ve verimliliği artırmak amacıyla yapay zeka destekli birçok otomatik immünofloresans sistemi geliştirilmiştir. Bu çalışmanın amacı, otomatik immünofloresans sistemi olan Concepta’nın, IIF yöntemi kullanılarak ANA testinde rutin klinik ortamlardaki performansını değerlendirmektir.
Gereç ve Yöntemler: iPRO işlemcisiyle hazırlanan toplam 1000 hasta serum örneği, Concepta otomatik sistemi kullanılarak analiz edildi. Sonuçlar, iki uzman klinisyen tarafından yapılan manuel değerlendirmelerle karşılaştırılarak sistemin uyumu, duyarlılığı, özgüllüğü ve patern tanımlama doğruluğu değerlendirildi.
Bulgular: Concepta sistemi, pozitif ve negatif ayrımda manuel değerlendirmelerle %98,11 genel uyum gösterdi ve κ değeri 0,958 olarak hesaplandı. Duyarlılık ve özgüllük sırasıyla %99,08 ve %97,61 olarak belirlenirken, pozitif prediktif değerleri ve negatif prediktif değerleri %87,96 ve %99,83 bulundu. Homojen (%95,7), sentromer (%92,3) ve nükleoler (%92,1) paternlerde yüksek uyum oranları gözlemlenirken, benekli (%60) ve sitoplazmik (%44,4) paternlerde uyum daha düşüktü.
Sonuç: Concepta otomatik sistemi, ANA pozitif ve negatif ayrımında diğer otomatik sistemlerle kıyaslanabilir oldukça yüksek bir doğruluk oranı sergiledi. Concepta sisteminin yoğun ince benekli ve mix paternlerin tanınmasında bazı sınırlılıkları bulunsa da özellikle pozitif ve negatif sonuçlar arasında ayrım yapmada gösterdiği başarı dikkat çekmektedir. Bu sonuçlar, Concepta sisteminin ANA testi alanında umut verici yeni bir alternatif olduğunu göstermektedir.

Keywords

Otoantikorlar, Antinükleer Antikor Testi, İmmünfloresan mikroskopi

Performance Assessment of the Concepta Automated ANA Detection System in Routine Clinical Samples

Abstract

Aim: Indirect immunofluorescence (IIF) on HEp-2 cells is the standard method for detecting anti-nuclear antibodies (ANA) due to its high sensitivity. Recently, several artificial intelligence-supported automated immunofluorescence systems have been developed to improve standardization and efficiency in ANA detection using the IIF method. This study aimed to evaluate the performance of the Concepta automated immunofluorescence system in routine clinical settings for ANA testing using the IIF method.
Material and Methods: A total of 1000 patient serum samples were analyzed using the Concepta automated system after preparation with the iPRO processor. The results were compared to manual evaluations conducted by two expert clinicians to assess the system's agreement, sensitivity, specificity, and accuracy in pattern recognition.
Results: The Concepta system demonstrated an overall agreement of 98.11% with manual evaluations for positive and negative discrimination, corresponding to a κ value of 0.958. The sensitivity and specificity were found to be 99.08% and 97.61%, respectively, with positive and negative predictive values of 87.96% and 99.83%. High concordance rates were observed for homogeneous (95.7%), centromere (92.3%), and nucleolar (92.1%) patterns, while lower rates were noted for speckled (60%) and cytoplasmic (44.4%) patterns.
Conclusion: The Concepta automated system demonstrated very high accuracy in ANA positive and negative discrimination, comparable to other automated systems. Despite some limitations in recognizing dense fine speckled and mixed patterns, it proved particularly effective in distinguishing between positive and negative results. These findings suggest that the Concepta system is a promising new alternative in the field of ANA testing.

Keywords

Autoantibodies, Antinuclear Autoantibodies, Immunofluorescence Microscopy

References

• Pisetsky DS. Pathogenesis of autoimmune disease. Nat Rev Nephrol. 2023;19(8):509-24.
• Tebo AE. Recent approaches to optimize laboratory assessment of antinuclear antibodies. Clin Vaccine Immunol. 2017;24(12):e00270-17.
• Bizzaro N, Antico A, Platzgummer S, Tonutti E, Bassetti D, Pesente F, et al. Automated antinuclear immunofluorescence antibody screening: A comparative study of six computer-aided diagnostic systems. Autoimmun Rev. 2014;13(3):292-8.
• Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch Pathol Lab Med. 2000;124(1):71-81.
• Damoiseaux J, Andrade LEC, Carballo OG, Conrad K, Francescantonio PLC, Fritzler MJ, et al. Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective. Ann Rheum Dis. 2019;78(7):879-89.
• Andrade LEC, Klotz W, Herold M, Musset L, Damoiseaux J, Infantino M, et al. Reflecting on a decade of the international consensus on ANA patterns (ICAP): Accomplishments and challenges from the perspective of the 7th ICAP workshop. Autoimmun Rev. 2024;23(9):103608.
• Infantino M, Meacci F, Grossi V, Manfredi M, Benucci M, Merone M, et al. The burden of the variability introduced by the HEp-2 assay kit and the CAD system in ANA indirect immunofluorescence test. Immunol Res. 2017;65(1):345-54.
• Cinquanta L, Bizzaro N, Pesce G. Standardization and quality assessment under the perspective of automated computer-assisted HEp-2 immunofluorescence assay systems. Front Immunol. 2021;12:638863.
• Kim J, Lee W, Kim GT, Kim HS, Ock S, Kim IS, et al. Diagnostic utility of automated indirect immunofluorescence compared to manual indirect immunofluorescence for anti-nuclear antibodies in patients with systemic rheumatic diseases: A systematic review and meta-analysis. Semin Arthritis Rheum. 2019;48(4):728-35.
• Mahler M, Meroni PL, Bossuyt X, Fritzler MJ. Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. J Immunol Res. 2014;2014:315179.
• van Beers JJBC, Hahn M, Fraune J, Mallet K, Krause C, Hormann W, et al. Performance analysis of automated evaluation of antinuclear antibody indirect immunofluorescent tests in a routine setting. Auto Immun Highlights. 2018;9(1):8.
• Li Z, Han R, Yan Z, Li L, Feng Z. Antinuclear antibodies detection: A comparative study between automated recognition and conventional visual interpretation. J Clin Lab Anal. 2019;33(1):e22619.
• Park Y, Kim SY, Kwon GC, Koo SH, Kang ES, Kim J. Automated versus conventional microscopic interpretation of antinuclear antibody indirect immunofluorescence test. Ann Clin Lab Sci. 2019;49(1):127-33.
• Yoo IY, Oh JW, Cha HS, Koh EM, Kang ES. Performance of an automated fluorescence antinuclear antibody image analyzer. Ann Lab Med. 2017;37(3):240-7.
• Loock CD, Egerer K, Feist E, Burmester GR. Automated evaluation of ANA under real-life conditions. RMD Open. 2017;3(1):e000409.
• Daves M, Blecken J, Matthias T, Frey A, Perkmann V, Dall´ Acqua A, et al. New automated indirect immunofluorescent antinuclear antibody testing compares well with established manual immunofluorescent screening and titration for antinuclear antibody on HEp-2 cells. Immunol Res. 2017;65(1):370-4.
• Durmuş MA, Kömeç S, Gülmez A. Artificial intelligence applications for immunology laboratory: image analysis and classification study of IIF photos. Immunol Res. 2024;72(6):1277-87.
• Hobson P, Lovell BC, Percannella G, Vento M, Wiliem A. Classifying anti-nuclear antibodies HEp-2 images: A benchmarking platform. 22nd International Conference on Pattern Recognition. 2014. p.3233-8.
• Hobson P, Lovell BC, Percannella G, Vento M, Wiliem A. Benchmarking human epithelial type 2 interphase cells classification methods on a very large dataset. Artif Intell Med. 2015;65(3):239-50.
• Boral B, Togay A. Automatic classification of antinuclear antibody patterns with machine learning. Cureus. 2023;15(9):e45008.
• Won DIL. Measurements of endpoint titers based on the fluorescence intensity trend in anti-nuclear antibody testing. Lab Med. 2020;51(5):469-77.
• Tebo AE. Recent Approaches to optimize laboratory assessment of antinuclear antibodies. Clin Vaccine Immunol. 2017;24(12):e00270-17.