Pre-clinical autoimmunity can reveal immune changes that initiate or prevent clinical disease. We reported that (i) 16% ANA-positive At-Risk individuals progressed to SLE/pSS in year 1; (ii) ANA-positive individuals without clinical disease have defective pDC function and non-haematopoietic interferon-production. Here we describe the immunophenotype of our ANA-positive cohort compared to healthy controls.
A prospective observational study of At-Risk individuals was conducted over 3 years. Annual follow up data was used to categorise patients as: ‘Progressors’ (classification criteria for SLE, pSS or other RMD); 'Undifferentiated autoimmune disease' (at least one clinical criterion but without progression); 'Benign autoreactivity' (no clinical criteria). Previously validated IFN-Scores and flow cytometry for major circulating subsets were analysed at baseline.
148/150 patients had 3-year follow up. Outcomes were: progressors: 30/148 (20%) [SLE=25; pSS=5]; Undifferentiated autoimmune disease: 51/148 (34%); Benign autoreactivity: 67/148 (45%).
Compared to healthy controls, Progressors had increased IFN-Score-A(p<0.001), IFN-Score-B(p=0.073), reduced monocytes(p=0.077), but increased naïve-B(p<0.001), transitional-B(p=0.014) and CD4 T-cells(p=0.018). Similarly, Undifferentiated autoimmune disease had increased IFN-Score-A(p=0.005), reduced monocytes(p=0.002), and increased naïve B(p<0.001), transitional B(p=0.014) and CD 4 T cells(p=0.018).
In patients with benign autoreactivity, despite no clinical criteria for RMD after 3 years, we found increased IFN-Score-A(p=0.090), reduced monocytes(p=0.066), increased naïve-B cells(p<0.001), transitional B-cells(p=0.046) and CD4 T-cells(p=0.032) similar to the other groups, but in contrast, this group also had significantly reduced CD8 T-cells(p=0.006).
Clinically benign ANA positivity is a complex immune state with features seen in SLE; pDC exhaustion, keratinocyte interferon production, increased blood interferon score, and disturbance of peripheral blood mononuclear cell (PBMC) subsets.