Name: Immunodeficiency 57 with autoinflammation | Acronym: IMD57
Alt. names: AR RIPK1 deficiency

Gene: RIPK1 | MOI: Autosomal recessive | Mechanism of action: Loss of Function

No. of cases in DB: 2 | First reported in: 2018

Last updated on: 2024-07-24 20:04:00 by Xiao P. Peng

OMIM: 618108

Orphanet: -

MONDO: -

DOID: -

ClinGen:

Biallelic RIPK1 LOF mutations have been linked to a syndrome of primary immunodeficiency with early-onset IBD and polyarthritis [OMIM: 618108] (PMID: 30026316). Patients have lymphopenia with defective T- and B-cell differentiation, explaining their susceptibility to recurrent viral, bacterial and fungal infections. Their cells show impaired NF-κB and MAPK signaling, increased necroptosis and dysregulated cytokine production - in particular, RIPK1-deficient patient cells showed reduced stimulation-induced production of most cytokines relative to controls except for increased IL-1β production in response to both LPS and PHA stimulation. Additional individuals with combined immunodeficiency and/or intestinal inflammation harboring biallelic missense (I615T, T645M, C601Y), frameshift and nonsense mutations were subsequently reported (PMID: 30591564, 31213653). Li et al. (2019) showed that at least some of the mutations were associated with reduced NF-kappaB activity, defective T- and B-cell differentiation, increased inflammasome activity, and impaired responses to TNFR1-mediated cell death in intestinal epithelial cells. It remains unclear if the severe motor delay and mild intellectual disability described for one Brazilian individual are attributable to RIPK1 deficiency (PMID: 31213653).

Preventative measures and early and aggressive treatment of infections (e.g., IVIG has been described as beneficial); HSCT has been reportedly successful in resolving immune-mediated problems and VEO-IBD in 1 patient. Refs. PMIDs: 30026316; 31827280; 31827281