OP0044 ANA POSITIVITY IS ASSOCIATED WITH COMPLEX IMMUNE DISTURBANCE EVEN IN INDIVIDUALS WHO DO NOT DEVELOP CLINICAL AUTOIMMUNE DISEASE
Authors: S. U. Hassan, Z. Wigston, A. Burska, M. Y. MD Yusof, E. Vital
Journal: Annals of the Rheumatic Diseases (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. Biomarker Healthy Controls Mean (95% CI) Non-progressors Mean (95% CI) Difference from healthy controls p Absolute non-progressors Mean (95% CI) Difference from healthy controls p Progressors Mean (95% CI) Difference from healthy controls p IFN 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) 0.001 IFN 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-cytes 14.80 (10.50, 19.11) 15.46 (12.96, 17.97) 0.187 14.94 (11.42, 18.47) 0.738 10.36 (7.42, 13.30) 0.227 % CD4 T cells 62.90 (57.75, 68.05) 64.89 (60.86, 68.92) 0.001 68.72 (62.97, 74.47) 0.267 60.93 (53.64, 68.21) 0.001 % CD8 T cells 32.18 (27.47, 36.90) 28.60 (25.12, 32.09) 0.135 25.02 (20.28, 29.77) 0.044 31.51 (25.63, 37.40) 0.875 % Naïve B cells 65.59 (56.56, 74.61) 73.74 (70.02, 77.46) 0.001 76.86 (72.21, 81.51) 0.128 68.86 60.62, 75.84) 0.173 % Memory B cells 29.56 (20.42, 38.72) 19.72 (15.84, 23.61) &lt;0.000 23.13 (16.65, 29.61) 0.054 25.57 (17.18, 33.96) 0.163 % Plasma-blasts 1.12 (0.81, 1.43) 0.91 (0.58, 1.24) 0.964 1.01 (0.44, 1.58) 0.457 0.81 (0.53, 1.10) 0.112 % NK cells 13.65 (9.65, 17.65) 12.30 (8.90, 15.71) 0.480 12.35 (6.65, 18.05) 0.781 11.90 (8.65, 15.14) 0.195 Conclusion: 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. 2020 Disclosure 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.