OP0044 ANA POSITIVITY IS ASSOCIATED WITH COMPLEX IMMUNE DISTURBANCE EVEN IN INDIVIDUALS WHO DO NOT DEVELOP CLINICAL AUTOIMMUNE DISEASE
Authors: Hassan S. U. , Wigston Z. , Burska A. , MD Yusof M. Y. , Vital E. 
Published: May 2021

Background:Study of pre-clinical autoimmunity can reveal immune changes that initiate or prevent clinical disease. We previously reported an At Risk cohort of ANA positive individuals referred to secondary care, of whom 16% progressed to SLE or Sjogren’s syndrome during follow up[1]. Recently, we also reported that even ANA positive individuals who do not develop clinical autoimmunity, have defective pDC function and non-haematopoietic interferon-production[2].Objectives:To describe the immunophenotype of ANA-positive progressors and non-progressors compared to healthy controls.Methods:We conducted a prospective observational longitudinal study of At-Risk individuals in Leeds (n=150) over 3 years with annual follow up. Those who met classification criteria for autoimmune connective tissue disease (AI-CTD) during follow up were termed progressors and others; non-progressors. Among the non-progressors, those with no clinical diagnostic criteria at any time point were called absolute non-progressors (ANP).At baseline we analysed two IFN-stimulated gene expression scores previously described[3] and flow cytometry performed for major circulating subsets. Association between progression group and biomarkers were tested using independent samples t-test.Results:3 year follow up data were available in 148/150 patients. Outcomes were: progressors: 30/148 (20%) [SLE=25; pSS=5] and non-progressors: 118/148 (80%). Within the non-progressors, 69/148 (47%) were ANP.A detailed analysis of baseline biomarkers is included in Table 1. Despite not developing clinically significant disease, non-progressors had significant alterations in several biomarkers. This was also evident in the ANP sub-group.Table 1.BiomarkerHealthy ControlsMean(95% CI)Non-progressorsMean(95% CI)Difference from healthy controlspAbsolute non-progressorsMean(95% CI)Difference from healthy controls pProgressorsMean (95% CI)Difference from healthy controls pIFN score A-6.27 (-6.88, -5.65)-5.22 (-5.64, -4.80)0.016-5.11 (-5.91, -4.32)0.120-4.14 (-5.11, -3.18)0.001IFN score B-5.43 (-6.00, -4.85)-5.30 (-5.62, -4.98)0.193-4.96 (-5.45, -4.47)0.949-4.27 (-4.90, -3.65)0.136% Mono-cytes14.80 (10.50, 19.11)15.46 (12.96, 17.97)0.18714.94 (11.42, 18.47)0.73810.36 (7.42, 13.30)0.227% CD4 T cells62.90 (57.75, 68.05)64.89 (60.86, 68.92)0.00168.72 (62.97, 74.47)0.26760.93 (53.64, 68.21)0.001% CD8 T cells32.18 (27.47, 36.90)28.60 (25.12, 32.09)0.13525.02 (20.28, 29.77)0.04431.51 (25.63, 37.40)0.875% Naïve B cells65.59 (56.56, 74.61)73.74 (70.02, 77.46)0.00176.86 (72.21, 81.51)0.12868.86 60.62, 75.84)0.173% Memory B cells29.56 (20.42, 38.72)19.72 (15.84, 23.61)<0.00023.13 (16.65, 29.61)0.05425.57 (17.18, 33.96)0.163% Plasma-blasts1.12 (0.81, 1.43)0.91 (0.58, 1.24)0.9641.01 (0.44, 1.58)0.4570.81 (0.53, 1.10)0.112% NK cells13.65 (9.65, 17.65)12.30 (8.90, 15.71)0.48012.35 (6.65, 18.05)0.78111.90 (8.65, 15.14)0.195Conclusion:Clinically benign ANA positivity is a complex immune state with many features seen in active SLE, including pDC exhaustion, keratinocyte interferon production and strong skin interferon score, increased blood interferon score, and disturbance of B cell subsets. These findings suggest that other factors are necessary for clinical disease, or that regulatory mechanisms stabilise autoimmunity. Further work in this cohort will address these questions.References:[1]Md Yusof et al. Ann Rheum Dis 2018[2]El-Sherbiny et al. Sci Rep 2018[3]Psarras et al. Nat Commun. 2020Disclosure of Interests:Sabih-Ul Hassan: None declared, Zoe Wigston: None declared, Agata Burska: None declared, Md Yuzaiful Md Yusof: None declared, Edward Vital Grant/research support from: Honoraria and research grant support from Roche, GSK and AstraZeneca.