Extended clinical phenotypes and treatment modalities in 32 JAGN1-deficient patients. A multicenter study by EBMT IEWP.

JAGN1 (Jagunal-homolog1) is a ER-resident transmembrane protein which is part of the early secretory pathway and granulocyte colony-stimulating factor receptor mediated signaling. Autosomal recessively inherited variants in the JAGN1 gene lead to congenital neutropenia, early-onset bacterial infections, aphthosis and skin abscesses due to aberrant differentiation and maturation of neutrophils. In addition, bone metabolism disorders and a syndromic phenotype, including facial features, short stature and neurodevelopmental delay, have been reported in affected patients.

Enforced CARD11/MALT1 signaling in dendritic cells triggers hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome fueled by uncontrolled mononuclear phagocyte activity, yet the innate immune mechanisms driving HLH pathogenesis remain elusive. Germline gain-of-function (GOF) mutations in CARD11, a pivotal regulator of lymphocyte antigen receptor signaling, cause the lymphoproliferative disease B-cell expansion with NF-κB and T-cell anergy, which is frequently associated with HLH development. Given that CARD11 is physiologically expressed not only in lymphocytes but also in dendritic cells (DCs), we explored whether enforced CARD11 signaling in DCs contributes to immunopathology.

Metabolomic profiles of infants classified as sudden infant death syndrome: a case-control analysis.

Background: Sudden Infant Death Syndrome (SIDS) is a leading cause of postneonatal mortality. The absence of specific biomarkers of SIDS diagnosis and risk leaves a significant gap in understanding SIDS pathophysiology. Metabolomics offers an avenue to better understand SIDS biology and identifying potential biomarkers.

Dupilumab in a 9-week-old with Netherton Syndrome Leads to Deep Symptom Control.

Purpose: Netherton syndrome (NS) is a rare inborn error of immunity (IEI) with an incidence of approximately 1:200,000 and the phenotypic triad of trichorrhexis invaginate (bamboo hair), congenital ichthyosiform erythroderma, and multiple atopic manifestations. Treatment options especially in infants are scarce and generally not licensed.

Methods: Case report of a 9-week-old infant with NS treated with dupilumab off-label.

The role of the primary healthcare research community in addressing the social and structural determinants of health: a call to action from NAPCRG 2023.

The need for effective primary healthcare to address social and structural determinants of health and to mitigate health inequalities has been well established. Here, we report on the international forum of the 2023 NAPCRG (formerly known as North American Primary Care Research Group) Annual Meeting. The aim of the forum was to develop principles for action for the primary healthcare research community on addressing social and structural determinants of health.