ANA Paternlerinin Dağılımı ve Klinik önemi: Türkiye’nin Doğu Bölgesinde 3744 hastanın Retrospektif analizi

Öz

Amaç: Antinükleer antikorlar (ANA), sistemik otoimmün romatizmal hastalıkların (AARD) tanısında başlıca serolojik belirteçlerden biridir. HEp-2 hücrelerinde indirekt immünofloresan (IIFA) yöntemi, farklı nükleer ve sitoplazmik paternlerin saptanmasına olanak sağlayarak ANA tespitinde altın standart kabul edilmektedir. Bu çalışmada, Türkiye’nin doğu bölgesinde geniş bir hasta kohortunda ANA pozitifliği, patern dağılımları ve klinik tanılarla ilişkisi değerlendirilmiştir. Yöntemler: Ocak–Aralık 2024 tarihleri arasında ANA testi yapılan 3.744 erişkin hasta retrospektif olarak incelenmiştir. Hastalar klinik tanılarına göre üç gruba ayrılmıştır: ANA ile ilişkili romatizmal hastalıklar (AARD), ANA ile ilişkili olmayan otoimmün hastalıklar (non-ANA-AID) ve klinik tanısı olmayan ANA pozitif olgular (ANA-NC). Bulgular: ANA pozitifliği genel olarak %14,8 (n=553) oranında saptanmıştır ve kadınlarda (%16,4) erkeklere (%10,0) göre anlamlı derecede yüksektir (p<0,001). Pozitiflik oranı yaşla birlikte artmıştır (p<0,001). En sık gözlenen nükleer paternler homojen (AC-1, %37,8), ince benekli (AC-4, %21,0), DFS-benzeri (AC-2, %16,3) ve nükleolar (AC-8–10, %12,1) olmuştur. Sitoplazmik pozitiflik %3,4 olup, retiküler (AC-21) patern baskındır (%63,3). Patern dağılımları hastalık gruplarına göre anlamlı farklılık göstermiştir (p<0,01). Homojen patern (AC-1) özellikle sistemik lupus eritematozus (SLE) ve romatoid artrit (RA) olgularında öne çıkmıştır. Sentromer paterni (AC-3) sistemik sklerozda (%60,6), ince benekli paterni (AC-4) Sjögren sendromunda (%61,4) baskındır. DFS-benzeri patern (AC-2) ANA-NC grubunda yüksek oranda (%71,1) görülmüş olup, bu paternin AARD dışlama belirteci olarak kullanılabileceğini göstermektedir. Sonuç: ANA pozitifliği RA’da sık görülse de, RA tanısında kriter olmamakla birlikte, klinik öneminin belirlenmesi için ileri araştırmalara ihtiyaç vardır. ANA testinin patern bazında değerlendirilmesi, otoimmün hastalıkların ayırıcı tanısında değerli bilgiler sağlamaktadır. Bölgesel hasta dağılımı, yaş ve cinsiyet farkları ile birlikte değerlendirildiğinde, çalışmamız Türkiye’nin doğu kesiminde ANA paternlerinin epidemiyolojisine ışık tutmaktadır.

Anahtar Kelimeler

• Romatizmal Hastalıklar
• Antinükleer Antikorlar
• Sistemik Lupus Eritematozus
• Romatoid Artrit; İmmünfloresans

Distribution and Clinical Significance of ANA Patterns: A Retrospective Analysis of 3744 Patients in Eastern Türkiye

Öz

Background: Antinuclear antibodies (ANA) are essential serological markers in the diagnosis of autoimmune rheumatic diseases (AARD). Indirect immunofluorescence assay (IIFA) using HEp-2 cells remains the gold standard for ANA detection, allowing simultaneous evaluation of nuclear and cytoplasmic patterns. This retrospective study aimed to determine the prevalence of ANA positivity, distribution of fluorescence patterns, and their clinical significance in a large patient cohort from Eastern Türkiye. Method: A total of 3,744 adult patients tested for ANA between January and December 2024 were analyzed. Patients were categorized into three groups: ANA-associated rheumatic diseases (AARD), non-ANA-associated autoimmune disorders (non-ANA-AID), and ANA-positive individuals without a definitive clinical diagnosis (ANA-NC). Results: Overall ANA positivity was 14.8% (n=553), significantly higher in women (16.4%) than in men (10.0%) (p<0.001), and increased with age (p<0.001). The most frequent nuclear patterns were homogeneous (AC-1, 37.8%), speckled (AC-4, 21.0%), DFS-like (AC-2, 16.3%), and nucleolar (AC-8–10, 12.1%). Cytoplasmic positivity was found in 3.4% of cases, predominantly with a reticular (AC-21) pattern (63.3%). Pattern distribution varied significantly among disease groups (p<0.01). The homogeneous pattern (AC-1) predominated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), while the centromere pattern (AC-3) was characteristic of systemic sclerosis and the fine speckled pattern (AC-4) was dominant in Sjögren’s syndrome. The DFS-like pattern (AC-2) was mostly observed in the ANA-NC group (71.1%), suggesting its potential role as an exclusion marker for AARD in clinical evaluation. Conclusion: ANA is not included among the diagnostic criteria for RA, its presence may have clinical implications, warranting further investigation. pattern-based ANA interpretation offers valuable diagnostic and differential insights into systemic autoimmune disorders. Our findings underline the importance of considering demographic factors such as gender and age when interpreting ANA results. This large-scale regional study contributes to the epidemiological understanding of ANA distribution and pattern prevalence in Eastern Türkiye and supports the integration of ICAP-based pattern recognition into routine diagnostic practice.

Anahtar Kelimeler

• Rheumatic Diseases
• Antinuclear Antibodies
• Systemic Lupus Erythematosus
• Rheumatoid arthritis
• Immunofluorescence.

Kaynakça

1. 1.Wei Q, Jiang Y, Xie J, et al. Analysis of antinuclearantibody titers and patterns by using HEp-2 andprimate liver tissue substrate indirectimmunofluorescence assay in patients withsystemic autoimmune rheumatic diseases. J Clin LabAnal. 2020;34:e23546.
2. 2.Bossuyt X, De Langhe E, Borghi MO, Meroni PL.Understanding and interpreting antinuclearantibody tests in systemic rheumatic diseases. NatRev Rheumatol. 2020;16:715-726.
3. 3.Andrade LEC, Klotz W, Herold M, et al. Reflectingon a decade of the international consensus on ANApatterns (ICAP): accomplishments and challengesfrom the perspective of the 7th ICAP workshop.Autoimmun Rev. 2024;23:103608.
4. 4.Damoiseaux J, Andrade LEC, Carballo OG, et al.Clinical relevance of HEp-2 indirectimmunofluorescent patterns: the InternationalConsensus on ANA patterns (ICAP) perspective. AnnRheum Dis. 2019;78:879-889.
5. 5.Kraev K, Hristov B, Uchikov P, et al.Comprehensive exploration of antinuclearantibodies (ANAs): unveiling clinical significance,associations with cancer, and the nuances ofdifferential diagnosis in positive ANA patients.Diagnostics (Basel). 2024;14.
6. 6.Tozzoli R, Bizzaro N, Tonutti E, et al. Guidelines forthe laboratory use of autoantibody tests in thediagnosis and monitoring of autoimmune rheumaticdiseases. Am J Clin Pathol. 2002;117:316-324.
7. 7.Lau KH, Do YT, Chan YH, et al. Evaluation of anti-nuclear antibodies (ANA) patterns for agingpopulation in Hong Kong. J Immunol.2021;206:21.20-21.20.
8. 8.Meier HCS, Sandler DP, Simonsick EM, Weng NP,Parks CG. Sex differences in the association betweenantinuclear antibody positivity with diabetes andmultimorbidity in older adults: results from theBaltimore Longitudinal Study of Aging. ExpGerontol. 2020;135:110906.

9. 9. Van Hoovels L, Broeders S, Chan EKL, et al. Currentlaboratory and clinical practices in reporting andinterpreting anti-nuclear antibody indirectimmunofluorescence (ANA IIF) patterns: results ofan international survey. Autoimmun Highlights.2020;11:17.
10. 10.Zanussi JT, Zhao J, Wei WQ, et al. Clinicaldiagnoses associated with a positive antinuclearantibody test in patients with and withoutautoimmune disease. BMC Rheumatol. 2023;7:24.
11. 11.Ramachandran A, Kumar K, Sankaralingam R,Chinnadurai S, Chilukuri B. A retrospective study onantinuclear antibody patterns in systemic lupuserythematosus patients and its correlation withserological markers. Cureus. 2023;15:e50049.
12. 12.Liu F, Wang XQ, Zou JW, Li M, Pan CC, Si YQ.Association between serum antinuclear antibodyand rheumatoid arthritis. Front Immunol.2024;15:1358114.
13. 13.Cavazzana I, Vojinovic T, Airo P, et al. Systemicsclerosis-specific antibodies: novel and classicalbiomarkers. Clin Rev Allergy Immunol.2023;64:412-430.
14. 14.Favoino E, Grapsi E, Barbuti G, et al. Systemicsclerosis and primary biliary cholangitis share anantibody population with identical specificity. ClinExp Immunol. 2023;212:32-38.
15. 15. Lundgren MC, Sapkota S, Peterson DJ, Crosson JT.The antinuclear antibody dense fine speckledpattern and possible clinical associations: anindication of a proinflammatory microenvironment.J Immunol Methods. 2021;488:112904.
16. 16.Yumuk Z, Demir M. Clinical value of anti-DFS70antibodies in a cohort of patients undergoingroutine antinuclear antibodies testing. J ImmunolMethods. 2020;480:112754.
17. 17.Seelig CA, Bauer O, Seelig HP. Autoantibodiesagainst DFS70/LEDGF exclusion markers for systemic autoimmune rheumatic diseases (SARD). Clin Lab. 2016;62:499-517.
18. 18.Conrad K, Rober N, Andrade LEC, Mahler M. Theclinical relevance of anti-DFS70 autoantibodies. ClinRev Allergy Immunol. 2017;52:202-216.
19. 19.Nakano K, Fujita S, Hiramatsu-Asano S, et al.Clinical significance of antinuclear antibodies inpatients with rheumatoid arthritis: from SETOUCHI-RA registry. J Clin Med. 2025;14.
20. 20.Van Leeuwen NM, Boonstra M, Bakker JA, et al.Anticentromere antibody levels and isotypes andthe development of systemic sclerosis. ArthritisRheumatol. 2021;73:2338-2347.
21. 21.Bernstein RM, Steigerwald JC, Tan EM.Association of antinuclear and antinucleolarantibodies in progressive systemic sclerosis. ClinExp Immunol. 1982;48:43-51.
22. 22.Reimer G, Steen VD, Penning CA, Medsger TAJ,Tan EM. Correlates between autoantibodies tonucleolar antigens and clinical features in patientswith systemic sclerosis (scleroderma). ArthritisRheum. 1988;31:525-532.
23. 23.Hesselstrand R, Scheja A, Shen GQ, Wiik A,Akesson A. The association of antinuclear antibodieswith organ involvement and survival in systemicsclerosis. Rheumatology (Oxford). 2003;42:534-540.