Unexpected Diagnosis of WHIM syndrome in Refractory Autoimmune Cytopenia.
Blood Adv
; 2024 Jul 19.
Article
en En
| MEDLINE
| ID: mdl-39028950
ABSTRACT
WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome is a rare primary immunodeficiency predominantly caused by heterozygous gain-of-function mutations in the c-terminus of the gene CXCR4. These CXCR4 variants display impaired receptor trafficking with persistence of the CXCR4 receptor on the surface resulting in hyperactive downstream signaling following CXCL12 stimulation. In turn, this results in defective lymphoid differentiation, and reduced blood neutrophil and lymphocyte numbers. Here we report a CXCR4 mutation that in two members of a kindred, led to life-long autoimmunity and lymphoid hypertrophy as the primary clinical manifestations of WHIM syndrome. We examine the functional effects of this mutation, and how these have affected phosphorylation, activation, and receptor internalization.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Blood Adv
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos