POS0128 THE RISK OF SYSTEMIC LUPUS ERYTHEMATOSUS REMAINS ELEVATED YEARS AFTER TESTING POSITIVE FOR ANTINUCLEAR ANTIBODIES: NATIONAL COHORT STUDY IN DENMARK
Authors: C. De Saint-Aubain, R. Westermann, K. B. Lauridsen, S. Kristensen, K. S. Duch, L. Dreyer
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Although the presence of antinuclear antibodies (ANA) is a prerequisite for classification of systemic lupus erythematosus (SLE), the predictive value of a positive ANA has not been well studied. <h3>Objectives:</h3> The aim of this study was to examine recorded blood samples for the presence of ANAs and the subsequent risk of developing SLE. <h3>Methods:</h3> We followed 341,756 Danish individuals without prior SLE diagnosis aged ≥18 years from date of first ANA laboratory test or January 1, 2000, until SLE diagnosis, death, or December 31, 2018. Data was obtained through linkage between laboratory data from Statens Serum Institute, the Danish Laboratory Database, and the National Patient Registry. SLE diagnosis was obtained using a validated algorithm. Three ANA methods were utilised in the study period: 1) ANA-screen (an assay using an ELISA-like technique targeting specific detection of 14 autoantibodies of known clinical importance), 2) ANA indirect immunofluorescence (IIF) (detects immunofluorescence on HEp-2 cells at serum dilution 1:160), and 3) ANA titre (titration analysis on HEp-2 cells performed at dilutions 1:160, 1:320, 1:640, 1:1280). Hazard ratios (HR) for SLE with 95% confidence intervals (CI) were calculated for ANA positive versus ANA negative individuals using Cox regression models with time since ANA test as the underlying time scale, adjusted for sex, birth year, test year and region of residence. <h3>Results:</h3> A total of 198,872 unique ANA-screen samples (706,049 person-years (PY) with a mean of 3.6 years of follow-up (FU)), 149,935 ANA-IIF samples (1,630,396 PY, mean 10.9 years of FU), and 11,312 ANA-titre samples (85,414 PY, mean 7.6 years of FU) were available. Of the 259,043 included individuals, mean age was 53.9 years with 233,171 (67.3 %) women. After sampling, 6.0% were ANA-screen positive, 15% ANA-IIF positive and 37% ANA-titre positive. During FU, a total of 813 individuals were diagnosed with SLE. A positive ANA-screen showed an HR of 67.4 for SLE (95% CI 45.8–99.1) compared to a negative ANA-screen. For ANA-IIF and ANA-titre, the risk of SLE was especially related to the homogenous and speckled pattern, but also to the nucleolar pattern. There was no relation between centromere, proliferating cell nuclear antigen, mitotic spindle, nuclear dots or coarse speckled nuclear patterns, and subsequent risk of SLE. The risk of SLE was especially high within the first year after a positive ANA-screen test (HR 67.4, 95% CI 45.8–99.1). The HRs remained high throughout the study period, but attenuated over time (Table 1). A positive ANA with a homogenous or speckled pattern also showed an increased risk of SLE within the first year for both ANA-IIF and ANA-titre. The risk was especially high for the homogenous pattern by ANA-IIF with an HR of 15.6 (95% CI 12.4–19.8) with a decreasing trend over time (Table 1). The risk remained elevated even after &gt;5 years of FU (HR 10.0, 95% CI 6.1–16.2), which was also the case with ANA-titre, and speckled pattern by ANA-IIF. While a positive ANA-screen showed a markedly increased risk of SLE, the absolute risk of SLE remained low compared to test for ANA-IIF or ANA-titre homogenous and speckled patterns (Figure 1). The absolute risk of SLE was highest for individuals with a positive homogenous or speckled pattern by ANA-titre. A negative test for an ANA-titre homogenous pattern showed the same level of absolute risk for SLE events as a positive ANA-screen (Figure 1A), with a similar trend for the speckled pattern (Figure 1B). <h3>Conclusion:</h3> In ANA-tested individuals, a positive ANA-screen, or a positive ANA with a homogenous, speckled or nucleolar pattern were associated with an increased risk of SLE. The hazard ratio for SLE was especially elevated within the first year after testing, although the hazard ratio for SLE remained elevated for at least 5 years after ANA test with a decreasing trend over time. The results are in agreement with previous studies indicating a prolonged preclinical phase, which should be considered when counselling patients regarding their risk of SLE development. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> The study was financially supported by the Danish Rheumatism Association. <h3>Disclosure of Interests:</h3> Constance de Saint-Aubain: None declared, Rasmus Westermann: None declared, Karen Buch Lauridsen: None declared, Salome Kristensen: None declared, Kirsten S. Duch: None declared, Lene Dreyer has received research grants (paid to her institution) from BMS and Abbvie outside the current manuscript. She is member of the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies.