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1 Accepted Manuscript Evaluation of the LIA-ANA-Profile-17S for the detection of autoantibodies to nuclear antigens Ahram Yi, Chang-Hoon Lee, Hee-Won Moon, Hanah Kim, Mina Hur, Yeo-Min Yun PII: S (17) DOI: doi: /j.clinbiochem Reference: CLB 9748 To appear in: Clinical Biochemistry Received date: 1 November 2017 Revised date: 27 March 2018 Accepted date: 28 March 2018 Please cite this article as: Ahram Yi, Chang-Hoon Lee, Hee-Won Moon, Hanah Kim, Mina Hur, Yeo-Min Yun, Evaluation of the LIA-ANA-Profile-17S for the detection of autoantibodies to nuclear antigens. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Clb(2018), doi: / j.clinbiochem This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2 Evaluation of the LIA-ANA-Profile-17S for the detection of autoantibodies to nuclear antigens Ahram Yi a*, Chang-Hoon Lee a*, Hee-Won Moon a, Hanah Kim a, Mina Hur a and Yeo-Min Yun a a Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Korea * These two authors equally contributed to this manuscript. Running title: Evaluation of LIA-ANA-Profile-17S Correspondence: Hee-Won Moon, M.D., Ph.D. Department of Laboratory Medicine Konkuk University School of Medicine Konkuk University Medical Center 120-1, Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul 05030, Korea Tel: , Fax: , hannasis@hanmail.net

3 Abstract Objectives: The diagnostic tests for autoimmune disease include screening for autoantibodies for nuclear antigens (ANA) and antibodies against extractable nuclear antigens (ENA). Using the line immunoassay (LIA) method, various kinds of ENA antibodies can be detected simultaneously. We evaluated the performance of the newly launched LIA-ANA-Profile-17S (Shenzhen YHLO Biotech, Shenzhen, China) as compared to a conventional LIA kit. Methods: Residual samples were collected from 200 patients who had been tested for ANA using indirect immunofluorescence. The LIA-ANA-Profile-17S was compared to the EuroLine ANA (Euroimmun, Oberlausitz, Germany) for the analysis of 17 different autoantibodies. The concordance rate and agreement between assays were determined. Samples showing discrepancies between the LIA-ANA-Profile-17S and EuroLine tests were further examined through additional analysis. Results: The overall agreement was moderate (kappa = 0.759, 95 % CI = ). Agreement between assays ranged from weak to almost perfect, except for those tests targeting nucleosomes, histones, and PM-Scl. Of the 57 disparate results between LIA-ANA- Profile-17S and EuroLine, 38 (66.7%) samples tested positive under an additional assay, showing variable patterns between types of autoantibodies. The positive rate of each autoantibody between LIA-ANA-Profile-17S and EuroLine did not differ significantly, except for anti-nucleosome and anti-histone assays in samples from patients diagnosed with systemic lupus erythematosus (P=0.004 and 0.001, respectively). Conclusions: Compared to those from the conventional EuroLine assay, the LIA-ANA- Profile-17S results showed variable agreement in samples showing different prevalence of each autoantibody. The most frequently detected antibodies showed almost perfect agreement. The LIA-ANA-Profile-17S could play a role in the diagnosis of systemic autoimmune disease in ANA-positive samples.

4 Key words: LIA-ANA-Profile-17S, ENA, Line immunoassay, EuroLine

5 1. Introduction Systemic rheumatic diseases are characterized by the presence of one or more autoantibodies for nuclear antigens (ANAs) or other cell components [1, 2]. Many rheumatic diseases have a distinctive profile of autoantibodies, with each ANA having a diagnostic and prognostic value. Various detection methods are in use to identify these profiles, and new techniques to facilitate diagnosis and therapeutic monitoring are being developed regularly. Detection of each autoantibody and the resulting clinical inferences varies according to the diagnostic technique or platform chosen [3]. Line immunoassays (LIAs) are commonly used to further characterize autoantibodies previously identified through screening tests such as indirect immunofluorescence (IIF)[4], and can be used as a primary test for detection of disease-specific autoantibodies. LIAs are easy to perform and have shown high sensitivity and specificity [5]. An important advantage of LIAs is their capacity for simultaneous detection of multiple autoantibodies using strips coated with several antigens; recent advances in automation also make them an appealing platform for high-throughput laboratories [6]. In this study, we evaluated the recently launched LIA-ANA-Profile-17S (Shenzhen YHLO biotech, Shenzhen, China) and compared it to the EuroLine LIA (Euroimmun, Oberlausitz, Germany), an assay commonly used for the detection of ANAs. 2. Material and Methods 2.1. Study population This study was approved by the institutional review board (KUH ) of the Konkuk University Medical Center, Seoul, Korea. Non-duplicated residual samples were collected from 200 patients who had tested for ANA using IIF. The characteristics of the

6 study population are summarized in Table 1. Samples were stored at 70 C until use. The data were analyzed anonymously, and this study required neither study-specific nor any other intervention; therefore, written informed consent from enrolled patients was exempted Assays LIA-ANA-Profile-17S is an indirect, membrane-based enzyme immunoassay for the qualitative determination of IgG antibodies against 17 antigens, comprising nucleosome, dsdna, histone, SmD1, PCNA, P0, SS-A/Ro60kD, Ro52/TRIM21, SS-B/La, CENP-B, Scl- 70, U1-snRNP, AMA-M2, Jo-1, PM-Scl, Mi-2, and Ku. These tests were performed using InnoCare Lab (Sugentech, Osong, Republic of Korea). The results were interpreted as negative, weakly positive, moderately positive, or strongly positive by comparing the intensity of the test lines with that of three control lines. The results from the LIA-ANA-Profile-17S were compared with those from the EuroLine ANA using EUROLine Master (Euroimmun). The EuroLine ANA is an LIA that provides a qualitative in vitro assay for 14 human IgG autoantibodies targeting nrnp, Sm, SS-A, SS-B, Scl-70, PM-Scl, Jo-1, CENP-B, PCNA, dsdna, nucleosome, histones, ribosomal P-protein, and AMA-M2. Signal intensities of 0 5, 6 10, 11 25, 26 50, and > 50 were interpreted as negative, borderline, positive, and strongly positive, respectively. In this study, weakly positive results in LIA-ANA-Profile-17S were considered positive and borderline results in EuroLine were considered negative. Samples that yielded discordant results when tested with LIA-ANA-Profile-17S and EuroLine were further assayed using: anti-dsdna (Trinity Biotech, Wicklow, Ireland); Anti-Centromere B (Orgentec, Mainz, Germany); the Scl-70, Sm, Sm/RNP, SS-A (Ro), SS-B (La), Jo-1 Test System (Zeus, New Jersey, USA); and the QUANTA Lite Histone ELISA (INOVA, San Diego, USA).

7 2.3. Statistical analysis Data are expressed as the median and interquartile range (IQR) or number and percentage. Agreement between assays was determined using Cohen s kappa coefficient, with measurements < 0.20, , , , , and > 0.90 indicating no, minimal, weak, moderate, strong, and almost perfect agreement, respectively [7]. Agreement between assays was calculated as any positive results versus negative results. Statistical analysis was performed using MedCalc Statistical Software (version 15.8, MedCalc Software, Mariakerke, Belgium) and IBM SPSS Statistics 22.0 (IBM Corporation, Armonk, NY, USA). P values less than 0.05 were considered statistically significant. 3. Results As shown in Table 2, the overall agreement between the LIA-ANA-Profile-17S and the EuroLine was moderate (kappa = 0.759, 95% CI = ), and showed a range of concordances from 93% to 99.5% for an overall rate of 96.8%. The anti-ss-a/ro60kd and CENP-B assays showed almost perfect agreement (kappa = and 0.974, respectively), while the anti-ss-b/la test displayed strong agreement (kappa = 0.808). Anti-SmD1, U1- snrnp, RPP/P0, Ro52/TRIM21, Jo-1 and AMA-M2 assays showed moderate agreement (kappa = 0.740, 0.743, 0.725, 0.791, 0.720, and 0.603, respectively). The anti-dsdna test yielded weak agreement (kappa = 0.467) (Table 2). The results of the additional tests performed on samples with divergent LIA-ANA- Profile-17S and EuroLine scores are presented in Table 3. Among the 57 reassessed samples, 38 (66.7 %) tested positive on another assay. For anti-dsdna, 83.3 % (10/12) of the samples that tested positive with LIA-ANA-Profile-17S and negative with EuroLine yielded positive results under the third test. The 85.7 % (12/14) of samples that were positive for the antihistone EuroLine assay and negative for the LIA-ANA-Profile-17S assay had positive results

8 in the third test. The 50.0 % (6/12) of anti-u1-snrnp samples that were negative under LIA- ANA-Profile-17S and positive for EuroLine had positive results in the third test. Patients with systemic autoimmune diseases comprised 84.2 % (48/57) of the 57 divergent samples. The positive results of autoantibodies from different disease populations, as determined by the LIA-ANA-Profile-17S and EuroLine assays, are presented in Table 4. The positive outcomes of each autoantibody did not differ significantly (P values were not less than 0.05) between the two techniques, except for the anti-nucleosome and anti-histone antibody in samples from patients diagnosed with SLE (P=0.004 and 0.001, respectively). 4. Discussion Until now, the IIF technique using HEp-2 cells has been the preferred screening test to identify autoantibodies for diagnosis of systemic rheumatic diseases. When an autoantibody is found by IIF, individual assays such as immunoprecipitation or ELISA are then used to confirm the autoantibody type. However, a negative IIF result cannot rule out the presence of various sorts of autoantibodies, including those directed against Ku, Jo-1, SS-A/Ro60, Ro52/TRIM21, SS-B/La, and RNA polymerases. Moreover, pattern assignment by manual IIF is time consuming, laborious and could be subjective [8]. Thus, the development of more sensitive assays is essential for cases where there is a high clinical suspicion of autoimmune disease [9, 10]. During the past decade, multiplex technologies have been developed for the simultaneous screening of multiple autoantibodies [3, 11, 12]. Early LIAs were mainly performed manually but automated, high throughput LIAs are now available [6]. The newly launched LIA-ANA-Profile-17S detects 17 autoantibodies simultaneously and has an automated platform. Although this type of platform is more expensive than IIF, the cost per antibody is lower than that of a single analyte test [13]. In this study, the kappa coefficient value for each autoantibody varied; by its nature,

9 kappa is influenced by the distribution of positive and negative samples. Frequently detected autoantibodies like anti-ss-a/ro60kd, CENP-B, and SS-B/La showed strong or almost perfect agreement. Although there are only a few dissimilar results, the low number of positive samples resulted in low kappa values for anti-sm, Scl-70, Jo-1, and AMA-M2. There were very few positive results for samples subjected to anti-nucleosome, histone, PCNA, and PM-Scl assays, so agreement could not be accurately assessed. This reflects a low prevalence of these autoantibodies in our sample population; more data is needed in order to evaluate the performance of these two techniques for the detection of these autoantibodies. For the EuroLine, based on the signal intensity compared with positive control, the results could be divided into negative, borderline, and positive results. If there is very weak band, results are considered as borderline based on manufacturer s insert. In this study, borderline results from the EuroLine were considered negative for agreement calculation. The anti-dsdna, SS-B/La, and Scl-70 assays showed weak, strong, and strong agreement, respectively (kappa= 0.47, 0.81, and 0.80). If borderline results from the EuroLine tests had been considered positive, then the anti-dsdna, SS-B/La, and Scl-70 outcomes would have shown minimal, moderate, and weak agreement (kappa= 0.38, 0.67, and 0.56, respectively) due to the increase of discordant results between the LIA-ANA-Profile-17S and the EuroLine platforms. By considering borderline results from the EuroLine as negative, we could reduce the number of results that differed between the systems. There were relatively a high number of samples with conflicting results for the antidsdna (14 discordant samples/200 total samples), nucleosome (11/200), histone (14/200), and U1-snRNP assays (13/200) (Table 3). In samples with divergent anti-dsdna outcomes, most showed a positive reading with the LIA-ANA-Profile-17S and a negative result under the EuroLine. Most of these samples (85.7%) read positive by radioimmunoassay (RIA). Many types of assays are available for

10 anti-dsdna, including RIA (Farr assay), IIF, and ELISA, yet there are significant differences between the class, avidity, complement-fixing ability, antigenic specificity, and cross-reactive patterns of these tests [14, 15]. A recent study showed anti-dsdna outcomes to be most frequently positive when using Farr and fluorescence immunoassays during active nephritis [16]. In our work, the LIA-ANA-Profile-17S seemed to be more sensitive than the EuroLine for anti-dsdna assays. However, disease activity is usually monitored through anti-dsdna readings using a single assay rather than an LIA. Most samples with conflicting results for anti-nucleosome, histone, U1-snRNP, and Ro52/TRIM21 assays read negative with the LIA-ANA-Profile-17S platform and positive with the EuroLine system. Considering clinical features and the results of additional tests performed on these samples, the EuroLine technology seems to be more sensitive for the detection of these autoantibodies (Table 3, 4) [17, 18]. The antigens used in the assays could be a cause of discrepancy, although various kits use the same antigen nomenclature. For example, the LIA-ANA-Profile-17S antigens for dsdna and nucleosomes are purified from calf thymus. The corresponding antigens for the equivalent EuroLine assays are purified from salmon testes and calf thymus, respectively. Discordances in detecting extractable nuclear antigen (ENA) autoantibodies may be attributed to subtle differences in the clone or type of antigen (recombinant or purified), solid-phase source of antigen, epitopes available for antibody binding, and the affinity of autoantibodies for those epitopes [19]. The positive results for each antibody as detected by the LIA-ANA-Profile-17S and EuroLine is shown in Table 4. Although the EuroLine kit showed a higher positive rate in the anti-nucleosome and histone assays of samples from patients with SLE than did the LIA- ANA-Profile-17S system, frequently detected antibodies showed similar prevalence in both assays. Anti-dsDNA and nucleosome positive results were fewer than previously published [18, 20, 21]. These antibodies have been associated with disease activity in SLE. Our study

11 included patients being treated for low-activity SLE, whereas previous studies predominantly focused on patients with an active form of the disease [18, 20, 21]. Further studies including patients with active SLE are needed before a correlation between disease and autoantibody presence can be determined. This study has several limitations. First, the number of patients in some of the disease categories, such as Sjogren s syndrome, systemic sclerosis, and myositis, was insufficient for accurate disease correlation and prevalence comparisons. Second, this evaluation was based on comparison between two assay platforms rather than to a gold standard assay, because there is not yet a definitive test for ENA by which all other assays are evaluated [22, 23]. We performed additional tests on discordant samples but could not determine true positive or negative results. Moreover, alternative tests for some antigens, such as nucleosomes, RPP/P0, Ro52/TRIM21, PM-Scl, and AMA-M2, were not available. This study, which centered on a small population and used limited testing, would benefit from the support of further studies complementing its limitations. In conclusion, the LIA-ANA-Profile-17S platform showed variable agreement, in samples showing different prevalence of each autoantibody when compared to the conventional EuroLine assay. The most frequently detected antibodies showed almost perfect agreement and similar prevalence. The LIA-ANA-Profile-17S could play a role in the diagnosis of systemic autoimmune disease in ANA-positive samples. Further studies encompassing a greater number of samples containing rarely detected autoantibodies are needed. Conflicts of interest statement There are no conflicts of interest.

12 Acknowledgments None. References [1] M. Satoh, M. Vazquez-Del Mercado, E. K. Chan, Clinical interpretation of antinuclear antibody tests in systemic rheumatic diseases. Modern rheumatology 19 (2009) [2] C. A. von Muhlen, E. M. Tan, Autoantibodies in the diagnosis of systemic rheumatic diseases. Seminars in arthritis and rheumatism 24 (1995) [3] M. J. Fritzler, Advances and applications of multiplexed diagnostic technologies in autoimmune diseases. Lupus 15 (2006) [4] J. Damoiseaux, K. Boesten, J. Giesen, J. Austen, J. W. Tervaert, Evaluation of a novel line-blot immunoassay for the detection of antibodies to extractable nuclear antigens. Ann N Y Acad Sci 1050 (2005) [5] Y. Kumar, A. Bhatia, R. W. Minz, Antinuclear antibodies and their detection methods in diagnosis of connective tissue diseases: a journey revisited. Diagn Pathol 4 (2009) 1. [6] F. J. Lopez-Longo et al., Simultaneous identification of various antinuclear antibodies using an automated multiparameter line immunoassay system. Lupus 12 (2003) [7] M. L. McHugh, Interrater reliability: the kappa statistic. Biochem Med (Zagreb) 22 (2012) [8] I. Y. Yoo, J. W. Oh, H. S. Cha, E. M. Koh, E. S. Kang, Performance of an Automated Fluorescence Antinuclear Antibody Image Analyzer. Ann Lab Med 37 (2017) [9] M. Mahler, J. T. Ngo, J. Schulte-Pelkum, T. Luettich, M. J. Fritzler, Limited reliability of

13 the indirect immunofluorescence technique for the detection of anti-rib-p antibodies. Arthritis Res Ther 10 (2008) R131. [10] M. J. Fritzler, The antinuclear antibody test: last or lasting gasp? Arthritis Rheum 63 (2011) [11] C. Bentow et al., Clinical performance evaluation of a novel rapid response chemiluminescent immunoassay for the detection of autoantibodies to extractable nuclear antigens. Clin Chim Acta 424 (2013) [12] M. J. Fritzler, M. L. Fritzler, The emergence of multiplexed technologies as diagnostic platforms in systemic autoimmune diseases. Curr Med Chem 13 (2006) [13] A. Man et al., An evaluation of autoimmune antibody testing patterns in a Canadian health region and an evaluation of a laboratory algorithm aimed at reducing unnecessary testing. Clin Rheumatol 32 (2013) [14] F. Fiegel et al., Autoantibodies to double-stranded DNA--intermethod comparison between four commercial immunoassays and a research biosensor-based device. Lupus 19 (2010) [15] D. A. Isenberg, J. J. Manson, M. R. Ehrenstein, A. Rahman, Fifty years of anti-ds DNA antibodies: are we approaching journey's end? Rheumatology (Oxford) 46 (2007) [16] K. de Leeuw, L. Bungener, C. Roozendaal, H. Bootsma, C. A. Stegeman, Autoantibodies to double-stranded DNA as biomarker in systemic lupus erythematosus: comparison of different assays during quiescent and active disease. Rheumatology (Oxford) 56 (2017) [17] Y. Sherer, A. Gorstein, M. J. Fritzler, Y. Shoenfeld, Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients. Seminars in arthritis and rheumatism 34 (2004)

14 [18] N. Bizzaro, D. Villalta, D. Giavarina, R. Tozzoli, Are anti-nucleosome antibodies a better diagnostic marker than anti-dsdna antibodies for systemic lupus erythematosus? A systematic review and a study of metanalysis. Autoimmun Rev 12 (2012) [19] T. G. Phan, R. C. Wong, S. Adelstein, Autoantibodies to extractable nuclear antigens: making detection and interpretation more meaningful. Clin Diagn Lab Immunol 9 (2002) 1-7. [20] W. Suer, C. Dahnrich, W. Schlumberger, W. Stocker, Autoantibodies in SLE but not in scleroderma react with protein-stripped nucleosomes. J Autoimmun 22 (2004) [21] Y. Su, R. L. Jia, L. Han, Z. G. Li, Role of anti-nucleosome antibody in the diagnosis of systemic lupus erythematosus. Clin Immunol 122 (2007) [22] M. Mahler, M. J. Fritzler, Epitope specificity and significance in systemic autoimmune diseases. Ann N Y Acad Sci 1183 (2010) [23] N. Agmon-Levin et al., International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis 73 (2014)

15 Table 1. Characteristics of the study population Variables All patients (N=200) * Age (years), median [IQR] 45[ ] Males, N (%) 54 (27.7) FANA titer, N (%) Negative 50 (25) Positive 1:80 52 (26) 1: (49) Diagnosis, N (%) SLE 60 (30.0) Systemic sclerosis 18 (9.0) Sjögren syndrome 16 (8.0) Myositis 8 (4.0) Rheumatoid arthritis 3 (1.5) Ankylosing spondylitis 2 (1.0) Other connective disease 14 (7.0) Non-autoimmune disease 79 (39.5) * Five patients with unknown age and sex were excluded from each item. More than half of patients with non-autoimmune disease consisted of dermatologic disease; the rest consisted of neurological, orthopedic, hepatic, and other diseases. Abbreviations: IQR, interquartile range; FANA, fluorescent antinuclear antibody test; SLE, systemic lupus erythematosus. Table 2. Agreement between the LIA-ANA-Profile-17S and the EuroLine

16 The results of LIA-ANA-Profile-17S & EuroLine Kappa LIA-ANA-Profile-17S Positive Positive Negative Negative (95% CI) EuroLine Positive Negative Positive Negative dsdna ( ) Nucleosome ( ) Histone ( ) SmD ( ) U1-snRNP ( ) RPP/P ( ) PCNA SS-A/Ro60kD ( ) Ro52/TRIM ( ) SS-B/La ( ) CENP-B ( ) Scl ( ) Jo ( ) PM-Scl AMA-M ( ) Total 3000 results ( ) Abbreviations: CI, Confidence interval. Table 3. Detailed results for samples with discrepant results between the LIA-ANA-Profile-17S and the EuroLine

17 Antibodies dsdna Histone SmD1 U1-snRNP SS-A/Ro60kD LIA-ANA- Profile-17S Euroline N ANA by IIF Positive Negative 12 Negative Positive 2 Positive Negative Positive 14 Positive Negative 3 Negative Positive 1 Positive 12 1:160 9 Positive 2 1:160 2 Positive 14 1: Positive 3 1:160 3 Positive 1 1:160 1 Positive 1 1:160 1 Negative 1 Positive 11 1:160 6 Positive results in another test (%) Positive Negative 1 Negative Positive 12 Autoimmune disease Disease N (%) 10 (83.3) SLE 10 (83.3) 2 (100.0) SLE 1 (50.0) 12 (85.7) 0 (0.0) SLE SS SLE MCTD 12 (85.7) 1 (7.1) 2 (66.7) 1 (33.3) 0 (0.0) SLE 1 (100.0) 0 (0.0) SLE 1 (100.0) 6 (50.0) SLE SS CTD 6 (50.0) 2 (15.4) 2 (15.4) Positive Negative Positive 2 0 (0.0) SLE 2 (100.0)

18 SS-B/La CENP-B Scl-70 Jo-1 Positive Negative 2 Negative Positive 2 Positive Negative Positive 1 Positive Negative Positive 2 Positive Negative Positive 3 Total 57 Positive 2 1:160 1 Positive 2 1:160 2 Positive 2 1:160 2 Positive 1 1:160 1 Positive 2 1:160 0 Positive 3 1:160 2 Negative 1 Positive 56 1: (50.0) SS 1 (50.0) 2 (100.0) SLE 1 (100.0) 1 (100.0) SLE 1 (100.0) 2 (100.0) SSc 1 (50.0) 2 (66.7) SLE 3 (100.0) 38 (66.7) Autoimmune disease 48 (84.2) Abbreviations: IIF, indirect immunofluorescence; SLE, systemic lupus erythematosus; SS, Sjögren syndrome; MCTD, Mixed connective tissue disease; CTD, Connective tissue disease; SSc, Systemic sclerosis. Table 4. Positive rates of autoantibodies in different disease cohorts Cohort N Positive results of LIA- ANA-Profile-17S, N (%) Positive results of EuroLine, N (%) P value *

19 Systemic autoimmune diseases (76.9) 108 (89.3) SLE 60 dsdna 16 (26.7) 8 (13.3) Nucleosome 1 (1.7) 11 (18.3) Histone 1 (1.7) 13 (21.7) SmD1 7 (11.7) 6 (10.0) U1-snRNP 19 (31.7) 24 (40.0) P0 5 (8.3) 8 (13.3) PCNA 0 0 SS-A/Ro60kD 21 (35.0) 23 (38.3) Ro52/TRIM21 16 (26.7) 22 (36.7) SS-B/La 4 (6.7) 5 (8.3) CENP-B 5 (8.3) 6 (10.0) Sjogren s syndrome 16 SS-A/Ro60kD 9 (56.3) 10 (62.5) Ro52/TRIM21 11 (68.8) 13 (81.3) SS-B/La 4 (25.0) 4 (25.0) Systemic sclerosis 18 CENP-B 12 (66.7) 12 (66.7) Scl-70 2 (11.1) 3 (16.7) Myositis 8 Jo-1 4 (50.0) 4 (50.0) FANA titer 200 Negative 50 0 (0.0) 2 (4.0) Positive 150 1: (30.8) 19 (36.5) : (77.6) 85 (86.7) * P values were calculated by Chi-squared test and Fisher s exact test.

20 Highlights LIA-ANA-Profile-17S showed variable agreement. They showed almost perfect agreement with EuroLine in frequently detected antibodies. The LIA-ANA-Profile-17S could play a role in the diagnosis of autoimmune disease.

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