Interplay between epigenetic and genetic alterations in inborn errors of immunity

Abstract

Inborn errors of immunity (IEIs) comprise a variety of immune conditions leading to infections, autoimmunity, allergy, and cancer. Some IEIs have no identified mutation(s), while others with identical mutations can display heterogeneous presentations. These observations suggest the involvement of epigenetic mechanisms. Epigenetic alterations can arise from downstream activation of cellular pathways through both extracellular stimulation and genetic-associated changes, impacting epigenetic enzymes or their interactors. Therefore, we posit that epigenetic alterations and genetic defects do not exclude each other as a disease-causing etiology. In this opinion, encompassing both basic and clinical viewpoints, we focus on selected IEIs with mutations in transcription factors that interact with epigenetic enzymes. The intricate interplay between these factors offers insights into genetic and epigenetic mechanisms in IEIs.

Keywords: epigenetics; inborn errors of immunity; primary immunodeficiencies; transcription factors.