New Review – The Complexity of Being A20: From Biological Functions to Genetic Associations

Daniella M. Schwartz, MD, from the UPMC Division of Rheumatology and Clinical Immunology, along with Urekha Karri, PhD, and Manuel Carpio Tumba, PhD, published a review in the Journal of Clinical Immunology that analyzed the biology, regulation, and roles of A20, which is a critical negative regulator of immune activation.

A20 targets key signaling molecules like TRAF6 and RIPK1 to reduce inflammatory reactions.

Overview:

The team reviewed mechanisms and pathways related to human inflammatory disease and assessed genetic associations with immunologic disorders, including autoimmune, autoinflammatory, and allergic diseases.

The team also reviewed the broad spectrum of clinical phenotypes associated with A20 haploinsufficiency, making note of the extreme variability and need for aggressive consideration of genetic testing.¹

Methods:

To provide an in-depth assessment of A20, they reviewed both PubMed and Google Scholar articles and found cases of A20 haploinsufficiency. In total, they identified 73 articles and abstracts that described 199 patients from 130 families.

Conclusion:

The review suggests that there is still a significant amount to learn about A20 and its application across the spectrum of rheumatologic diseases and that continued research around this regulator is needed. Specifically, the researchers call for further investigation of haploinsufficiency and related diseases and certain mechanisms underlying some functions of various proteins.¹

View the full review and detailed conclusions from the research team.

Reference

1. Karri U, Harasimowicz M, Carpio Tumba M, Schwartz DM. The Complexity of Being A20: From Biological Functions to Genetic Associations. J Clin Immunol. 2024 Mar 7;44(3):76. doi: 10.1007/s10875-024-01681-1. PMID: 38451381.