Differential autoantibodies to cytokines in unselected patients with immune dysregulation 9195

Abstract Description Immune dysregulation occurs in multiple conditions characterized by inappropriate immune responses towards foreign or self-antigens. Rather than distinct categories of immunodeficiencies, autoimmune, or autoinflammatory disorders, these conditions represent a continuous spectrum with overlapping mechanisms. The role of cytokine-targeted autoantibodies across this spectrum remains incompletely understood but neutralizing anti-cytokine autoantibodies have recently been described in patients with AIRE-deficiency and as an explanation for severe infections such as SARS-CoV-2 pneumonia. We analyzed autoantibody profiles using a custom protein microarray platform in a diverse cohort of 34 patients (23 females, 11 males) with various forms of immune dysregulation. Our cohort encompassed monogenic autoinflammatory disorders, systemic autoimmune and conditions, and unclear manifestations of systemic immune dysregulation. We compared anti-cytokine antibody profiles against pre-pandemic healthy controls, post-pandemic healthy controls, and APS-1 patients known to harbour multiple anti-cytokine autoantibodies. Principal component analysis revealed distinct autoantibody signatures, predominantly characterized by differential reactivity against interferons and other key cytokines. Lesser-known autoantibodies to interleukins (IL22, IL17F, IL1F6) and immune regulators (CCL13, SERPINC1) were novel findings in selected patients of immune dysregulation. Funding Sources PhD position supported financially by Barncancerfonden Topic Categories Immune Mechanisms of Human Disease (HUM)