Allergy & Immunology

Grass pollen SLIT dampens type 2 CD4+ responses early with durable benefit despite stable specific IgE

Moderate to severe seasonal allergic rhinitis patients received standardized grass pollen SLIT for three years. Within one year, frequencies of IL-4/IL-13–producing and CD154-expressing CD4+ T cells decreased, while IFN-γ–producing CD4+ T cells remained stable. Patients experienced significant, long-term clinical improvement in rhinitis symptoms over the treatment course. Grass pollen–specific IgE levels stayed relatively stable, despite the durable clinical benefit and attenuated type 2 CD4+ responses. 1

PPAR-γ–regulated macrophage senescence drives murine allergic airway inflammation and is reversible with rosiglitazone

In a cockroach allergen asthma model, single-cell RNA sequencing showed enhanced senescence signatures in mononuclear phagocytes, with elevated Cdkn2a (p16). Senescent cell clearance with dasatinib plus quercetin reduced airway inflammation and Th2 cytokines, including IL-4 and IL-5. Macrophage-lineage PPAR-γ deletion worsened airway inflammation and senescence, implicating PPAR-γ as a protective regulator. Rosiglitazone reduced allergen-induced macrophage senescence and inflammatory mediators in vitro and ameliorated airway inflammation in vivo. 2

Isolated IgG and combined IgG/IgM deficiencies show milder, distinct phenotypes compared with CVID

This retrospective cohort compared clinical and immunologic features of CVID, isolated IgG deficiency, and combined IgG/IgM deficiency in primary hypogammaglobulinemia. Respiratory and gastrointestinal infections were less frequent in isolated IgG and combined IgG/IgM deficiencies than in CVID, whereas mucocutaneous HSV reactivation was more common. CVID patients more often had immune dysregulation manifestations, including splenomegaly and immune thrombocytopenic purpura, with markedly worse overall survival. Immunophenotyping showed lower class-switched memory B cells in CVID, while IgG deficiency patients had reduced transitional B cells. 3

VEXAS: UBA1-mutant adult autoinflammatory syndrome at the crossroads of clonal hematopoiesis and systemic inflammation

This narrative review summarizes epidemiology, pathogenesis, clinical spectrum, diagnostics, and treatment of VEXAS syndrome using registry and literature data. VEXAS arises from somatic UBA1 mutations, typically at codon 41, and predominantly affects older males. Patients often present with relapsing polychondritis, cytopenias, neutrophilic dermatoses, and overlap with myelodysplastic syndromes. Diagnosis is confirmed by demonstrating a somatic UBA1 mutation, integrating hematologic and rheumatologic assessment. Glucocorticoids are commonly used initially, but longer-lasting benefits are reported with JAK inhibitors, hypomethylating agents, or stem-cell transplantation. 4