JHI is a Gold Open Access journal that publishes papers that provide novel insights into the physiology and pathology of human immunity through the study of genetic defects and their phenocopies
This multiple-case study explores the burdens of illness, caregiving, and treatment for five families with children with severe leukocyte adhesion deficiency, type I (LAD-I). It highlights the experiences of nine caregivers and describes the ways their lives are impacted by this rare inborn error of immunity.
Samra, Sharma, et al. identify biallelic loss-of-function variants in OSMR as the cause of a new human primary atopic disorder characterized by severe early-onset eczema, eosinophilia, and elevated IgE. Loss of OSMRβ surface expression abolishes OSM-dependent STAT signaling, revealing a key role for OSM-OSMR signaling in maintaining cutaneous immune homeostasis.
Patients with STAT2 p.R148Q variant present with life-threatening neuroinflammation, respiratory failure, and high mortality rate. Early genetic recognition and treatment with high-dose JAK inhibitors may improve outcomes in this devastating but potentially treatable interferonopathy.
Suri et al. from PGIMER, Chandigarh, India, report large vessel vasculopathy as a rare, life-threatening, and underrecognized complication of Wiskott–Aldrich syndrome, often mimicking Takayasu arteritis. They implicate immune dysregulation, endothelial injury, and viral triggers, emphasizing early vascular screening and timely definitive therapy to reduce high mortality.
Allogeneic processed thymus tissue-agdc (RETHYMIC) is approved therapy for treatment of congenital athymia. Study outcomes include changes in T lymphocyte subsets and T cell function. Immune reconstitution was not associated with T cell function, immune suppression, or HLA matching. Younger age at implantation was associated with improved immune reconstitution.
CD55 deficiency drives complement hyperactivation, severe gastrointestinal pathology, and disrupted B cell homeostasis. Our findings show that complement inhibition in CHAPLE disease restores serum immunoglobulin levels, re-establishes a normal B cell profile, and enables effective humoral protection and optimal vaccine responses.
Christine Karanja-Chege, David Mwakisha Mwashigadi et al.
Karanja-Chege et al. describe a rare case of gastrointestinal tuberculosis in a severely immunosuppressed three-month-old infant presenting with intestinal obstruction in Kenya. Despite surgery and intensive care, life-threatening complications develop. The report underscores the diagnostic challenges, need for early recognition, immunodeficiency evaluation, and clearer management guidance for this severe condition.
The hyper IgE syndrome (formerly also called Job syndrome or Buckley syndrome) is a rare and syndromic primary immunodeficiency. It is an autosomal-dominant disorder caused by heterozygous dominant-negative mutations in the transcription factor STAT3. Here, we propose clinical management guidelines for this multisystem condition based on the experience and management of these patients in the last 25+ years.
Modi et al. review how primary atopic disorders, a group of monogenic inborn errors of immunity, reveal fundamental mechanisms regulating allergic inflammation. These human diseases show how disruptions in barrier integrity, immune signaling, cytoskeletal dynamics, and immune tolerance converge to drive severe type 2 inflammation and inform emerging precision therapies.
Li et al. present a comprehensive clinical framework for diagnosing and managing HA20, an immune dysregulation disease caused by loss-of-function TNFAIP3 variants. The authors outline clinical evaluation strategies, family screening, and phenotype- and biomarker-guided treatment strategies using IL-1, TNF, and JAK inhibitors.
