Swamy et al. describe an Australian/New Zealand cohort where identification of monogenic inborn errors of immunity through next-generation sequencing resulted in management change in 84% of cases, including guiding hematopoietic stem cell transplants and initiating targeted treatment. Molecular diagnosis further enabled diagnoses of affected relatives, underscoring the value of early genomic testing in inborn errors of immunity.

We report two cases of ADA-SCID complicated by severe hepatic manifestations, including hepatoblastoma and infantile hepatic hemangiomatosis. These cases highlight the challenges of multidisciplinary management and the need to modify definitive corrective therapies, including gene therapy and hematopoietic stem cell transplantation, in children with complex liver disease.

Galli, Recher et al. describe two patients with hypogammaglobulinemia associated with myotonic dystrophy type 1 (DM1), a rare and underdiagnosed monogenic neuromuscular disorder. The authors present clinical and immunophenotypic clues to aid clinical immunologists in making a correct diagnosis, while discussing the knowns and unknowns in the molecular pathogenesis of DM1-related antibody deficiency.

Patel et al. describe an elderly woman with severe chronic neutropenia caused by mosaic TLR8 gain-of-function. The report broadens a primarily pediatric, male disease spectrum and highlights somatic mosaicism as an important diagnostic consideration in adults with unexplained cytopenia and immune dysregulation.

Dethier et al. describe a young girl with SAVI on prolonged JAK inhibitors who developed fatal Aspergillus endocarditis. This report illustrates the major therapeutic challenges in STING1 gain-of-function disorders due to their intrinsic immunological abnormalities and highlights the need for more targeted alternatives such as anifrolumab.

AOSD is challenging to diagnose. Chong et al. examine the clinical utility of skin biopsy, an inexpensive and widely available test, in 16 patients with AOSD. They demonstrate that dyskeratotic keratinocytes in the superficial layers are useful for diagnosing AOSD.

The prevalence of autoantibodies neutralizing type I IFNs is significantly higher in Japanese patients with hepatitis C (2.7%) than in age-matched healthy controls (0.7%) and is even higher in those treated with IFN-α (3.9%) than in untreated individuals (1.9%).