Central nervous system autoimmunity and autoinflammation: insights from inborn errors of immunity

The landscape of inborn errors of immunity (IEIs) is rapidly broadening thanks to advancements in genetics and molecular diagnosis. This has led to an ever growing number of novel diseases discovered, but also to the expansion of genotype-phenotype correlations for specific defects. Among others, central nervous system (CNS) inflammation and autoimmunity have emerged as features of several distinct IEIs, arising from different pathophysiologic mechanisms. They include classic systemic autoinflammatory disorders, like periodic fevers, NF-κB and inflammasome defects; type I interferonopathies, such as Aicardi-Goutières syndrome (AGS) and pseudo-TORCH; vasculopathies, such as ADA2 deficiency and STING-associated vasculopathy with onset in infancy (SAVI); hemophagocytic lymphohistiocytosis (HLH); immune dysregulation syndromes, like FOXP3 deficiency, CTLA4 and LRBA deficiency, STAT1 and STAT3 gain-of-function; and immune defects causing CNS infections and inflammation, such as type I interferon defects, TLR3-pathway defects, COPA deficiency, and RANBP2 deficiency.

Besides providing a diagnosis for children and adults affected by neuroinflammatory disorders, the study of IEIs underlying neuroinflammation also helps advance our understanding of the immune-CNS crosstalk and of possible therapeutic targets, which could be then extended also to acquired neuroinflammatory conditions.

This research topic explores novel findings in known and novel IEIs underlying neuroinflammation, ranging from the validation of clinical and genetic features to the unraveling of the molecular mechanisms regulating the immune-neuro crosstalk and the inflammation, to the development of targeted therapy for these disorders.

We welcome the submission of Original Research, Review, Mini-review, Perspective, and Case Report articles covering, but not limited to, the following subtopics:

- Neuroinflammatory phenotypes associated with monogenic IEIs

- Novel genetic causes of neuroinflammation and CNS autoimmunity

- New insights on the molecular pathways involved in neuroinflammation

- Key cell types and cytokines underlying neuroinflammation in specific IEIs

- Potential therapeutic targets for these conditions

Topic Editor Dr. Christopher Duncan discloses consultancy for Moderna and Synairgen. The other Topic Editors declare no competing interests with regard to the Research Topic subject.