Genome-wide association study reveals an association between the HLA-DPB1∗02:01:02 allele and wheat-dependent exercise-induced anaphylaxis.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a life-threatening food allergy triggered by wheat in combination with the second factor such as exercise. The identification of potential genetic risk factors for this allergy might help high-risk individuals before consuming wheat-containing food. We aimed to identify genetic variants associated with WDEIA. A genome-wide association study was conducted in a discovery set of 77 individuals with WDEIA and 924 control subjects via three genetic models. The associations were confirmed in a replication set of 91 affected individuals and 435 control individuals. Summary statistics from the combined set were analyzed by meta-analysis with a random-effect model. In the discovery set, a locus on chromosome 6, rs9277630, was associated with WDEIA in the dominant model (OR = 3.95 [95% CI, 2.31-6.73], p = 7.87 × 10-8). The HLA-DPB1∗02:01:02 allele displayed the most significant association with WDEIA (OR = 4.51 [95% CI, 2.66-7.63], p = 2.28 × 10-9), as determined via HLA imputation following targeted sequencing. The association of the allele with WDEIA was confirmed in replication samples (OR = 3.82 [95% CI, 2.33-6.26], p = 3.03 × 10-8). A meta-analysis performed in the combined set revealed that the HLA-DPB1∗02:01:02 allele was significantly associated with an increased risk of WDEIA (OR = 4.13 [95% CI, 2.89-5.93], p = 1.06 × 10-14). Individuals carrying the HLA-DPB1∗02:01:02 allele have a significantly increased risk of WDEIA. Further validation of these findings in independent multiethnic cohorts is needed.

Real-world efficacy of proactive maintenance treatment with delgocitinib ointment twice weekly in adult patients with atopic dermatitis.

Previous studies have shown the efficacy of delgocitinib (DEL) ointment, a topical Janus kinase inhibitor, against atopic dermatitis (AD). However, there is no available information regarding the efficacy of DEL ointment in maintaining remission. Data of patients with AD who received remission maintenance therapy twice weekly with DEL or topical corticosteroid (TCS) on the affected skin of each upper limb were extracted from the medical records. Efficacy was assessed based on changes in pruritus numerical rating scale (NRS) score, stratum corneum hydration (SCH), erythema index (EI). Of 25 patients, four patients (16%) had eczema flare-ups on the TCS side and eight patients (32%) on the DEL side. The extent of change in each parameter between TCS- and DEL-treated areas of the skin did not differ significantly. The mean changes in the NRS and EI showed a slight improvement on the side treated with TCS and were slightly worse on the side treated with DEL. However, the SCH of the DEL group was maintained, while that of the TCS group worsened. TCS is more likely to be effective than DEL in terms of remission maintenance therapy. However, topical DEL is as effective as topical steroid in the maintenance therapy of AD in dry skin patients.

A Staphylococcus epidermidis strain inhibits the uptake of Staphylococcus aureus derived from atopic dermatitis skin into the keratinocytes.

BACKGROUND: Various bacterial species form a microbiome in the skin. In the past, dead Staphylococcus aureus derived from atopic dermatitis (AD) are taken up by keratinocytes; however, whether live S. aureus can be taken up by keratinocytes is unknown. OBJECTIVE: This study aimed to examine whether live AD strains of S. aureus internalize into the keratinocytes and how the internalization changes under conditions in which other bacterial species including S. epidermidis are present. METHODS: HaCaT cells were cultured with live S. aureus and S. epidermidis (live or heat-treated) or their culture supernatants. After coculture, the change in the amount of S. aureus in the cytoplasm of HaCaT cells was analyzed using, a high-throughput imaging system, Opera Phenix™. RESULTS: Live S. aureus were taken up in the cytoplasm of HaCaT cells. Coculturing live S. aureus with live S. epidermidis or the culture supernatants decreased the abundance of S. aureus in the cytoplasm. The heat-treated culture supernatants of live S. epidermidis or culture supernatants of other S. strains did not decrease the abundance of S. aureus in the cytoplasm. CONCLUSION: Live S. aureus was internalized into the cytoplasm of HaCaT cells as does heat-treated S. aureus. In addition, the heat-sensitive substances secreted by coculture with S. epidermidis and keratinocytes inhibited the uptake of S. aureus by keratinocytes.

Oncostatin M suppresses IL31RA expression in dorsal root ganglia and interleukin-31-induced itching.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intermittent itchy rash. Type 2 inflammatory cytokines such as interleukin (IL)-4, IL-13, and IL-31 are strongly implicated in AD pathogenesis. Stimulation of IL-31 cognate receptors on C-fiber nerve endings is believed to activate neurons in the dorsal root ganglion (DRG), causing itch. The IL-31 receptor is a heterodimer of OSMRß and IL31RA subunits, and OSMRß can also bind oncostatin M (OSM), a pro-inflammatory cytokine released by monocytes/macrophages, dendritic cells, and T lymphocytes. Further, OSM expression is enhanced in the skin lesions of AD and psoriasis vulgaris patients. Objective: The current study aimed to examine the contributions of OSM to AD pathogenesis and symptom expression. Methods: The expression levels of the OSM gene (OSM) and various cytokine receptor genes were measured in human patient skin samples, isolated human monocytes, mouse skin samples, and mouse DRG by RT-qPCR. Itching responses to various pruritogens were measured in mice by counting scratching episodes. Results: We confirmed overexpression of OSM in skin lesions of patients with AD and psoriasis vulgaris. Monocytes isolated from the blood of healthy subjects overexpressed OSM upon stimulation with IL-4 or GM-CSF. Systemic administration of OSM suppressed IL31RA expression in the mouse DRG and IL-31-stimulated scratching behavior. In contrast, systemic administration of OSM increased the expression of IL-4- and IL-13-related receptors in the DRG. Conclusion: These results suggest that OSM is an important cytokine in the regulation of skin monocytes, promoting the actions of IL-4 and IL-13 in the DRG and suppressing the action of IL-31. It is speculated that OSM released from monocytes in skin modulates the sensitivity of DRG neurons to type 2 inflammatory cytokines and thereby the severity of AD-associated skin itch.