Anti-cytokine autoantibodies: mechanistic insights and disease associations

Anti-cytokine autoantibodies (ACAAs) are increasingly recognized as modulating disease severity in infection, inflammation and autoimmunity. By reducing or augmenting cytokine signalling pathways or by altering the half-life of cytokines in the circulation, ACAAs can be either pathogenic or disease ameliorating. The origins of ACAAs remain unclear. Here, we focus on the most common ACAAs in the context of disease groups with similar characteristics. We review the emerging genetic and environmental factors that are thought to drive their production. We also describe how the profiling of ACAAs should be considered for the early diagnosis, active monitoring, treatment or sub-phenotyping of diseases. Finally, we discuss how understanding the biology of naturally occurring ACAAs can guide therapeutic strategies. This Review covers the biology of anti-cytokine autoantibodies and their varied roles in causing, preventing and treating diseases. Recent reports of anti-type I interferon autoantibodies in critical COVID-19 have led to renewed interest in this topic, which offers fascinating insights into the reversibility of immune tolerance and the origins of autoimmunity in otherwise healthy individuals.