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¹ Department of Pathology and Department of Medicine and Allied, The Indus Hospital and Health Network (IHHN), Karachi, Pakistan. [email protected].

² Department of Pathology, The Indus Hospital and Health Network (IHHN), Karachi, Pakistan.

¹ Department of Pathology and Department of Medicine and Allied, The Indus Hospital and Health Network (IHHN), Karachi, Pakistan. [email protected].

² Department of Pathology, The Indus Hospital and Health Network (IHHN), Karachi, Pakistan.

The diagnosis of systemic autoimmune diseases (SAID) is challenging, due to overlapping features with other non-immune disorders. Anti-nuclear antibodies (ANA)/anti-cellular antibodies are the sensitive screening tests but anti-double-stranded-deoxyribonucleic acid-antibody (anti-ds-DNA) and ANA-specific antibodies are specific for SAID. We aimed to look at ANA-specific antibodies in our patients and correlated them with ANA patterns, anti-ds-DNA, and clinical diagnosis for proper interpretation and better patient management cost-effectively. A retrospective data analysis of 641 patients was done (1st of February 2019 to 31st of July 2021) who were tested for ANA-specific antibodies at the Immunology Department of Indus Hospital and Health Network. ANA and anti-ds-DNA results and clinical diagnosis were also analyzed for ANA-specific antibody-positive patients. Descriptive data were presented in mean ± standard deviation and frequency percentages whereas inferential data were analyzed with a chi-square test for association between ANA-specific antibodies status, ANA, anti-ds-DNA, and clinical features. ANA-specific antibodies test revealed positivity for at least one autoantibody in 245 (38.2%) patients. Of these, ANA was tested in 206 patients reactive for ANA-specific antibodies and found positive in 195 (95%) as compared to negative (< 0.001). Speckled and homogenous were predominant ANA patterns in ANA-specific antibody-positives (56% and 42% respectively). Multiple ANA patterns were found in 18 patients most commonly with systemic lupus erythematosus (SLE) and mixed connective tissue disorder (MCTD). Anti-SSA were the most common ANA-specific antibodies (50%) and were mostly found in sera with speckled (61/97) and homogenous (38/97) patterns and associated mostly with SLE (48%) and Sjogren's syndrome (86%). Among ANA-negative patients, anti-SSA were the most common antibodies (n = 5). Anti-ds-DNA was found in 66% of SLE patients along with another ANA-specific antibody. This study showed that testing for ANA-specific antibodies cannot be gated on ANA patterns. Also, there is a redundancy of these antibodies with various clinical diagnoses. Moreover, they are useful in making a diagnosis in ANA-negative patients as well with clinical suspicion. Bremer HD, et al. Vet Immunol Immunopathol. 2015 Dec 15;168(3-4):233-41. doi: 10.1016/j.vetimm.2015.10.002. Epub 2015 Oct 9. Vet Immunol Immunopathol. 2015. PMID: 26547884 Rösken GHJ, et al. Ned Tijdschr Geneeskd. 2020 Apr 23;164:D4066. Ned Tijdschr Geneeskd. 2020. PMID: 32324347 Vermeersch P, et al. Autoimmun Rev. 2013 Aug;12(10):998-1003. doi: 10.1016/j.autrev.2013.03.014. Epub 2013 Apr 11. Autoimmun Rev. 2013. PMID: 23583982 Seelig CA, et al. Clin Lab. 2016;62(4):499-517. doi: 10.7754/clin.lab.2015.150905. Clin Lab. 2016. PMID: 27215068 Cao J, et al. Front Mol Biosci. 2025 Apr 14;12:1586294. doi: 10.3389/fmolb.2025.1586294. eCollection 2025. Front Mol Biosci. 2025. PMID: 40297850 Free PMC article. Zhu Q, et al. Front Microbiol. 2024 Apr 2;15:1295378. doi: 10.3389/fmicb.2024.1295378. eCollection 2024. Front Microbiol. 2024. PMID: 38628865 Free PMC article. Abozaid HSM, et al. Clin Rheumatol. 2023 Jul;42(7):1819-1826. doi: 10.1007/s10067-023-06577-w. Epub 2023 Apr 4. Clin Rheumatol. 2023. PMID: 37016193 Free PMC article. Yu HH, et al. Biomedicines. 2023 Nov 11;11(11):3027. doi: 10.3390/biomedicines11113027. Biomedicines. 2023. PMID: 38002026 Free PMC article. Missoum H, Alami M, Bachir F, Arji N, Bouyahya A, Rhajaoui M, El Aouad R, Bakri Y. Prevalence of autoimmune diseases and clinical significance of autoantibody profile: data from National Institute of Hygiene in Rabat. Morocco Hum Immunol. 2019;80(7):523–32. https://doi.org/10.1016/j.humimm.2019.02.012 . Garcia-Reyero J, Martinez Magunacelaya N, Gonzalez de Villambrosia S, Loghavi S, Gomez Mediavilla A, Tonda R, Beltran S, Gut M, Pereña Gonzalez A, d’Ámore E, Visco C, Khoury JD, Montes-Moreno S. Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma. Haematologica. 2021;106(4):1120–8. https://doi.org/10.3324/haematol.2020.251579 .