Publications by authors named "H E KENNEY"
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.
View Article and Find Full Text PDFRheumatoid arthritis (RA) is characterized by erosive pathology associated with joint inflammation and a sexual dimorphism with increased prevalence in females. Here, we aim to determine whether androgen is protective against inflammatory-erosive disease in TNF-transgenic (TNF-Tg) mice. Wild-type (WT) and TNF-Tg male mice underwent sham (WT, n = 3; TNF-Tg, n = 7) or orchiectomy (WT, n = 3; TNF-Tg, n = 7) surgery at 1 month old to remove androgen production confirmed by serum testosterone concentration.
View Article and Find Full Text PDFCERS1 is a biomarker of Staphylococcus aureus abundance and atopic dermatitis severity.
J Allergy Clin Immunol
September 2024
Article Synopsis
- Atopic dermatitis (AD) is an inflammatory skin condition linked to varying levels of Staphylococcus aureus, which affects disease severity and responds to treatments like dupilumab.
- This study aimed to identify host genes related to S aureus levels and AD severity using data from a clinical trial involving 71 adults with moderate-to-severe AD.
- The findings revealed a positive correlation between CERS1 expression (a gene associated with skin lipids) and both S aureus abundance and AD severity, suggesting CERS1 could serve as a biomarker for skin barrier dysfunction, with changes observable after dupilumab treatment.
Article Synopsis
- The study investigates a specific genetic variant in the IP3 receptor that results in a significant disorder affecting multiple systems, characterized by immunodeficiency and disturbed calcium release in cells.
- The variant (c.7570C>T, p.Arg2524Cys) leads to cellular defects, particularly impacting T cells, and is shown to affect calcium regulation and mitochondrial function, evidenced in laboratory models.
- Patients exhibited a range of symptoms beyond immunodeficiency, such as ectodermal dysplasia and short stature, suggesting that this genetic mutation plays a unique and broader role in disease compared to previously documented cases.
Rheumatoid arthritis (RA) is a complex immune-mediated inflammatory disorder in which patients suffer from inflammatory-erosive arthritis. Recent advances on histopathology heterogeneity of RA synovial tissue revealed three distinct phenotypes based on cellular composition (pauci-immune, diffuse and lymphoid), suggesting that distinct etiologies warrant specific targeted therapy which motivates a need for cost effective phenotyping tools in preclinical and clinical settings. To this end, we developed an automated multi-scale computational pathotyping (AMSCP) pipeline for both human and mouse synovial tissue with two distinct components that can be leveraged together or independently: (1) segmentation of different tissue types to characterize tissue-level changes, and (2) cell type classification within each tissue compartment that assesses change across disease states.
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