Background: Dermatophagoides farinae (Df ) is a major source of over 30 allergens that elicit allergic sensitization in atopic individuals. Despite its global significance, limited data exist on its allergenic relevance among a subset of Filipinos. Objectives: This study aimed to characterize the sensitization profile of a subset of Filipino allergic participants with elevated total immunoglobulin epsilon (IgE) (≥100 IU/mL) and to evaluate the associations between Df -specific IgE levels and demographic variables. An exploratory assessment of recombinant Der f 1 (rDer f 1) was also performed in a subset of samples. Methods: Plasma samples were obtained from participants with self-reported allergic asthma (AA), allergic rhinitis (AR), and/or atopic dermatitis (AD) (n = 690) and participants without self-reported allergies (n = 270), totaling 960 participants. Cases included participants with self-reported AA, AR, and/or AD and a total IgE level of ≥100 IU/mL, which served as a secondary screening criterion, resulting in 169 cases. Controls included participants without self-reported allergies and with a total IgE level of <100 IU/mL, resulting in 77 controls. Selected samples were analyzed for Df -specific IgE. rDer f 1-specific IgE enzyme-linked immunosorbent assay (ELISA) was performed in a subset (n = 90; 45 cases and 45 controls), while inhibition ELISA was conducted in 5 selected samples. Associations between Df -specific IgE positivity and demographic variables were assessed using Pearson correlation. Results: Allergic cases exhibited significantly higher mean total IgE levels (220.36 IU) than nonallergic controls (38.95 IU; P < 0.0001). Among allergic samples, 78.70% (133/169) were sensitized to Df , and all Df -positive samples (45/45) reacted to the rDer f 1 allergen. Df -specific IgE levels correlated significantly with allergy diagnosis ( P = 0.002), smoking status ( P = 0.004), and family history of atopy ( P = 0.040). Pre-absorption with rDer f 1 resulted in mean inhibition of 17% and maximum inhibition of 47% of IgE reactivity to Df extract. Conclusion: Df represents a clinically relevant allergen source within the subset of Filipino allergic patients, with rDer f 1 contributing to IgE reactivity among samples tested. These results suggest potential value in incorporating Df into diagnostic evaluation and future therapeutic considerations. Moreover, the findings remain exploratory and are constrained by limited sample size and study design.
As a first-line therapy for hyperuricemia, allopurinol is a recognized cause of severe drug reactions. While screening for the HLA-B*58:01 risk allele is recommended in certain Asian populations, individuals from other ancestries may also possess susceptibility alleles. A 68-year-old Filipino woman developed Drug Reaction with Eosinophilia and Systemic Symptoms following reinitiation of allopurinol, despite a history of long-term tolerance. Approximately 3 months after reinitiation, she presented with a progressive pruritic eruption, eosinophilia, and acute kidney injury. Discontinuing allopurinol and starting prednisone improved renal function and resolved eosinophilia. Human leukocyte antigen genotyping identified both HLA-B*58:01 and HLA-A*33:03 , alleles associated with allopurinol-induced severe cutaneous adverse reactions and reported in several Asian populations, including Filipinos. The patient completed a prednisone taper with full resolution of symptoms. This case highlights the need to consider pharmacogenetic risk factors beyond traditionally targeted ethnic groups and demonstrates that this reaction may develop after reinitiation with dose escalation of allopurinol, despite earlier tolerance.
Background: 15(S)-HETE, a bioactive lipid mediator derived from arachidonic acid, is closely associated with eosinophilic inflammation and recurrence in chronic rhinosinusitis with nasal polyps (CRSwNP). Nevertheless, its impact on fibroblast-associated transcriptional regulation remains poorly characterized. Objective: To characterize the transcriptional and immunologic alterations in fibroblasts following 15(S)-HETE exposure. Methods: Human fibroblasts (MRC-5) were exposed to either 15(S)-HETE or a dimethyl sulfoxide vehicle control before RNA sequencing. Differential expression analysis was combined with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation to characterize functional alterations. Pathway-level transcriptional changes were additionally explored using gene set enrichment analysis and weighted gene co-expression network analysis. Fibroblast viability was further assessed with a Cell Counting Kit-8 assay. Results: Transcriptomic profiling of the 15(S)-HETE-treated group revealed 96 differentially expressed genes, consisting of 54 upregulated and 42 downregulated genes. Upregulated genes were enriched in cytokine-related and inflammatory pathways, particularly interleukin-17 and tumor necrosis factor signaling. In contrast, downregulated genes were mainly involved in interferon-mediated antiviral responses. Gene set enrichment analysis further revealed significant suppression of interferon-α and interferon-γ response signatures. Weighted Gene Co-expression Network Analysis identified inflammation-related gene modules associated with 15(S)-HETE stimulation, in which CXCL1 was upregulated. In addition, 15(S)-HETE treatment significantly increased fibroblast viability. Conclusion: 15(S)-HETE was associated with changes in fibroblast transcriptional programs, including reduced interferon-related signatures and increased cytokine signaling. These findings suggest a potential role for 15(S)-HETE in fibroblast-associated immune regulation relevant to CRSwNP.
Background: Allergic rhinitis (AR) is an inflammation of the nasal mucosa primarily mediated by antigen-specific immunoglobulin E (IgE) and characterized predominantly by type 2 inflammation, in which the Janus kinase–signal transducer and activator of transcription (JAK-STAT) signaling pathway plays a critical role. Targeted inhibition of this pathway using small-molecule JAK inhibitor nasal sprays may represent a promising therapeutic strategy for AR. Objective: To evaluate the pharmacological profiles of pumecitinib (aka PG-011), a JAK inhibitor formulated as a nasal spray, for the treatment of AR in a mouse model. Methods: The inhibitory activity and selectivity of pumecitinib against JAK kinases were assessed in enzymatic assays. Its effects on cytokine-induced STAT phosphorylation (pSTAT) were evaluated in cellular assays. The pharmacological effects of pumecitinib nasal spray were investigated in an ovalbumin (OVA)-induced AR mouse model. Results: Pumecitinib was identified as a potent and selective inhibitor of JAK1 and JAK2 kinases relative to JAK3 and TYK2. It effectively suppressed pSTAT production induced by multiple cytokines, including interleukin (IL)-4, IL-31, and granulocyte-macrophage colony-stimulating factor. In the OVA-induced AR model, intranasal administration of 0.1% pumecitinib spray significantly reduced the frequency of sneezing episodes, as well as markedly attenuated nasal mucosal epithelial thickness, goblet cell hyperplasia, and eosinophil infiltration. The 0.05% concentration also produced significant reductions in epithelial thickness and eosinophil count. Both concentrations significantly lowered OVA-specific IgE levels in nasal lavage fluid. Conclusion: These findings demonstrate that pumecitinib nasal spray, through targeted inhibition of JAK1/2 kinases, exhibits pharmacological activity in a mouse model of AR, supporting its potential as a therapeutic candidate for further translational investigation in AR.
