Abstract
Introduction: Antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) on HEp-2 cells are a diagnostic hallmark of systemic lupus erythematosus (SLE). Specific patterns are linked to clinical manifestations. Data on ANA patterns and their clinical correlations in South Asian populations, particularly Nepal, remain limited.
Methods: This hospital-based cross-sectional study included 167 SLE patients (≥16 years) diagnosed by 2019 EULAR/ACR criteria. ANA testing was performed using IIF on HEp-2 cells, with patterns classified according to ICAP. Clinical data and immunological markers (anti-dsDNA, ENAs) were collected. Statistical analysis used Chi-square tests, with p < 0.05 considered significant.
Results: Among 167 patients (82% female, median age 39 years), the most prevalent patterns were nuclear homogeneous (NH; 45.5%), nuclear fine speckled (NFS; 25.7%), and nuclear coarse speckled (NCS; 16.8%). NH significantly associated with arthritis (p = 0.02), non-scarring alopecia (p = 0.03), lupus nephritis (p = 0.02), thrombocytopenia (p = 0.02), direct Coombs test (p = 0.04), anti-dsDNA (p < 0.001), anticardiolipin IgG (p = 0.03), lupus anticoagulant (p = 0.01), anti-histone (p = 0.01), and anti-nucleosome antibodies (p < 0.001). NFS associated with malar rash (p = 0.01). Anti-Sm/RNP and anti-RNP 68 strongly associated with NCS (p < 0.001 for both).
Conclusions: This study reveals specific ANA patterns and their significant clinical and immunological associations in Nepalese SLE patients. The NH pattern correlates strongly with severe manifestations such as lupus nephritis and with multiple autoantibodies, highlighting the importance of ANA pattern analysis for diagnosis and risk stratification.
Supplementary Files
References
1. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736-45. PMID: 30926722 DOI: https://doi.org/10.1136/annrheumdis-2019-215089
2. Pisetsky DS, Lipsky PE. New insights into the role of antinuclear antibodies in systemic lupus erythematosus. Nat Rev Rheumatol. 2020;16(10):565-79. PMID: 32884126 DOI: https://doi.org/10.1038/s41584-020-0480-7
3. Mariz HA, Sato EI, Barbosa SH, Rodrigues SH, Dellavance A, Andrade LEC. Pattern on the antinuclear antibody–HEp‐2 test is a critical parameter for discriminating antinuclear antibody–positive healthy individuals and patients with autoimmune rheumatic diseases. Arthritis Rheum. 2011;63(1):191-200. PMID: 20954189 DOI: https://doi.org/10.1002/art.30084
4. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PLC, et al. Report of the first international consensus on standardized nomenclature of antinuclear antibody HEp-2 Cell patterns 2014–2015. Front Immunol. 2015;6:412. PMID: 26347739 DOI: https://pubmed.ncbi.nlm.nih.gov/26347739/
5. Abeles AM, Abeles M. The clinical utility of a positive antinuclear antibody test result. Am J Med. 2013;126(4):342-8. PMID: 23395534 DOI: https://doi.org/10.1016/j.amjmed.2012.09.014
6. Satoh M, Chan EK, Ho LA, Rose KM, Parks CG, Cohn RD, et al. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis & Rheum. 2012;64(7):2319-27. PMID: 22237992 DOI: https://doi.org/10.1002/art.34380
7. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey‐Goldman R, et al. 2019 European league against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019;78(9):1151-59. PMID: 31383717 DOI: https://doi.org/10.1136/annrheumdis-2018-214819
8. Jafri SA, Ahsan T, Rida E Zehra S, Sultan S. Various manifestations of systemic lupus erythematosus (SLE) presenting at the rheumatology clinic in Southern Pakistan. Journal of Medical Sciences. 2019;27(3):225–9. Available from: https://jmedsci.com/Jmedsci/article/view/738
9. Infantino M, Bizzaro N, de Melo Cruvinel W, Chan EKL, Andrade LEC. Adopting the International Consensus on ANA Patterns (ICAP) classification for reporting: the experience of Italian clinical laboratories. Clinical Chemistry and Laboratory Medicine (CCLM). 2024;62(5):830-4. PMID: 37852014 DOI: https://doi.org/10.1515/cclm-2023-0752
10. Barber MRW, Drenkard C, Falasinnu T, Hoi A, Mak A, Kow NY, et al. Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol. 2021;17(9):515-32. PMID: 34345022 DOI: https://doi.org/10.1038/s41584-021-00668-1
11. Tseng YW, Lin CL, Chen SY, Er TK. Epidemiological analysis of antinuclear antibodies positivity and pattern distribution in a taiwanese hospital-based cohort. Br J Biomed Sci. 2025;82:15625. PMID: 41473536 DOI: https://doi.org/10.3389/bjbs.2025.15625
12. Frodlund M, Dahlström Ö, Kastbom A, Skogh T, Sjöwall C. Associations between antinuclear antibody staining patterns and clinical features of systemic lupus erythematosus: analysis of a regional Swedish register. BMJ Open. 2013;3(10):e003608. PMID: 24163206 DOI: https://doi.org/10.1136/bmjopen-2013-003608
13. Al-Mughales JA. Anti-Nuclear antibodies patterns in patients with systemic lupus erythematosus and their correlation with other diagnostic immunological parameters. Front Immunol. 2022;13:850759. PMID: 35359932 DOI: https://doi.org/10.3389/fimmu.2022.850759
14. Angel J, Thomas M, Appalaraju B. Evaluation of ELISA and indirect immunofluorescence in the diagnosis of autoimmune diseases and their interpretation in the clinical situation. J Acad Clin Microbiol. 2015;17(1):7-11. DOI: https://doi.org/10.4103/0972-1282.158776
15. 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. PMID: 24868563 DOI: https://doi.org/10.1155/2014/315179
16. Damoiseaux J, von Mühlen CA, Garcia-De La Torre I, Carballo OG, De Melo Cruvinel W, Francescantonio PLC, et al. International consensus on ANA patterns (ICAP): the bumpy road towards a consensus on reporting ANA results. Auto immun Highlights. 2016;7(1):1. PMID: 26831867 DOI: https://doi.org/10.1007/s13317-016-0075-0
17. Wang F, Wang CL, Tan CT, Manivasagar M. Systemic lupus erythematosus in Malaysia: a study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups. Lupus. 1997;6(3):248-53. PMID: 9104731 DOI: https://doi.org/10.1177/096120339700600306
18. Betancur JF, Londoño A, Estrada VE, Puerta SL, Osorno SM, Loaiza A, et al. Uncommon patterns of antinuclear antibodies recognizing mitotic spindle apparatus antigens and clinical associations. Medicine. 2018 Aug;97(34):e11727. PMID: 30142759 DOI: https://doi.org/10.1097/md.0000000000011727
19. Liu X, Xiao Z, Zhang X, Li J, Yuan Y, Li N, et al. A multi-dimensional risk signature for lupus nephritis in systemic lupus erythematosus: integrating symptoms, biochemistry and immune cell profiles. Front Immunol. 2025;16:1680747. PMID: 41280900 DOI: https://doi.org/10.3389/fimmu.2025.1680747
20. Suryajaya B, Moenardi V, Hidayat II, Hamijoyo L. 236 Anti-nuclear antibody pattern and clinical manifestation presentation in systemic lupus erythematosus. Lupus Science & Medicine. 2017;4(Suppl 1):A108.2-A108. DOI: https://doi.org/10.1136/lupus-2017-000215.236
21. Ramachandran A, Kumar K, Sankaralingam R, Chinnadurai S, Chilukuri B. A Retrospective study on antinuclear antibody patterns in systemic lupus erythematosus patients and its correlation with serological markers. Cureus. 2023;15(12):e50049. PMID: 38186533 DOI: https://doi.org/10.7759/cureus.50049
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