Multicenter international cohort study of HA20 reveals novel genetic architecture and phenotypic evolution - PubMed
7 days ago
- #TNFAIP3
- #immune dysregulation
- #HA20
- Multicenter international cohort study on Haploinsufficiency of A20 (HA20) involving 185 patients from 41 clinics across 7 countries.
- Common clinical features include mucocutaneous involvement (80.5%), recurrent fever (63.3%), gastrointestinal symptoms (58.6%), cytopenias (56.6%), arthritis/arthralgia (46.7%), and recurrent infections (35.5%).
- Intestinal ulcers were more frequent in children and Chinese cohort patients, while uveitis was less common in these groups.
- Two major disease phenotypes identified: autoinflammation-predominant and autoimmune-predominant, with the former more common in children and Chinese cohort patients.
- 89 pathogenic TNFAIP3 mutations identified, including 46 novel variants. Large deletions linked to neurologic disease and developmental delay.
- TNF and IL-1 inhibitors were effective treatments, with thalidomide and JAK inhibitors used in refractory cases. 51.5% achieved minimal disease activity at follow-up.
- HA20 is a dominantly inherited immune dysregulation disorder with phenotypic heterogeneity and potential age-dependent evolution.