A Basophil-Neuronal Axis Promotes Itch

Wang, Fang; Trier, Anna M.; Li, Fengxian; Kim, Seonyoung; Chen, Zhe; Chai, Jiani N.; Mack, Madison R.; Morrison, Stephanie A.; Hamilton, Jennifer D.; Baek, Jeong‐Heum; Yang, Ting-Lin B.; Heul, Aaron M. Ver; Xu, An; Xie, Zili; Dong, Xintong; Kubo, Masato; Hu, Hongzhen; Hsieh, Chyi-Song; Dong, Xinzhong; Liu, Qin; Margolis, David J.; Ardeleanu, Marius; Miller, Mark J.; Kim, Brian

doi:10.2139/ssrn.3624459

Cited by 22 publications

(47 citation statements)

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“…The pathophysiology of itch in eczema is not fully understood. Besides mast cell-histamines axis, basophiles are involved in acute itch flares, and many cytokines have also been identified, such as IL-4, IL-13, and substance P [ 48 , 49 ]. The current study showed that the VAS score of the RZC group reduced significantly compared with the placebo group and the no oral treatment group, indicating that RZC as an oral CHM is able to relieve itch effectively.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Runzao Zhiyang Capsule as an Add-On Therapy for Chronic Eczema: A Systematic Review and Meta-Analysis

Zhou

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Runzao Zhiyang capsule (RZC), an oral Chinese herbal medicine, has been widely used for chronic eczema in China for many years. This study aims to evaluate the efficacy and safety of RZC as an add-on therapy to conventional treatment for chronic eczema. Methods. Randomized controlled trials (RCTs) assessing the efficacy and safety of RZC as an add-on therapy for chronic eczema were retrieved from eight literature databases from their inception to 31 August, 2020, including CNKI, WanFang, VIP, Sinomed, PubMed, Cochrane Library, Web of Science, and Embase. The Cochrane risk of bias tool was used to assess the methodological quality of the included studies. The data were analyzed by RevMan5.3 software. Results. A total of 18 RCTs involving 1896 patients with chronic eczema were included. Compared with no oral treatment, RZC was superior on the total efficacy rate (TER) (RR = 1.45, 95% CI: 1.23 to 1.72, P < 0.0001 ), Eczema Area and Severity Index (EASI) (MD = −0.73, 95% CI: −0.90 to −0.56, P < 0.00001 ), and Visual Analogue Scale (VAS) for pruritus (MD = −2.76, 95%CI: −4.53 to −0.99, P = 0.002 ). Similar results were also seen in a randomized, placebo-controlled trial. Compared with the antihistamine (AH) group, TER in the RZC combined with AH group was significantly higher (RR = 1.32, 95% CI: 1.21 to 1.43, P < 0.00001 ), and the EASI score (MD = −0.29, 95% CI: −0.38 to −0.20, P < 0.001 ), the VAS score (MD = −0.19, 95% CI: −0.23 to −0.15, P < 0.00001 ), and the level of serum total IgE (MD = −9.83 ng/ml, 95% CI: −11.66 to −8.00 ng/ml, P < 0.00001 ) decreased more significantly in the RZC combined with AH group. In terms of safety, mild gastrointestinal diseases occurred more frequently in the RZC group, and no serious adverse effect was reported. Conclusions. RZC as an add-on therapy to conventional treatment shows good effects on chronic eczema, and there is no severe side effect from short-term use of RZC. However, due to suboptimal quality of the included studies, more large-sample and high-quality RCTs are needed to improve the evidence quality.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Runzao Zhiyang Capsule as an Add-On Therapy for Chronic Eczema: A Systematic Review and Meta-Analysis

Zhou

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…TSLP, IL-4, and IL-13 also act on the sensory nerve to potentiate chronic itch [ 34 ]. Itch can be triggered by several pruritogens, including histamine, IL-31, or leukotrienes [ 34 , 35 , 36 ]. Scratching will perpetuate a chronic inflammation and an epidermal barrier dysfunction by mechanically disrupting the skin outer layers.…”

Section: Atopic Dermatitis: a Multifactorial Pathogenesismentioning

confidence: 99%

“…Very recently, the Brian Kim lab showed in a preprint publication that, in an atopic context in mice, IgE mediated mast cell histamine release was not a primary determinant of acute itch induction, as it was at a steady state. In this model, antigen-mediated IgE crosslinking induced a basophil (but not mast cell) that derived release of cysteinyl leukotrienes able to induce acute itch flares through direct effects on sensory neurons [ 36 ]. Thus, if leukotrienes receptor antagonists have shown only controversial efficacy to treat eczema so far, new generations of antagonists could be new leads to reduce itch flares in AD patients [ 135 ].…”

Section: Consequences Of Ige Autoreactivitymentioning

confidence: 99%

IgE Autoreactivity in Atopic Dermatitis: Paving the Road for Autoimmune Diseases?

Pellefigues

2020

Antibodies

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Atopic dermatitis (AD) is a common skin disease affecting 20% of the population beginning usually before one year of age. It is associated with the emergence of allergen-specific IgE, but also with autoreactive IgE, whose function remain elusive. This review discusses current knowledge relevant to the mechanisms, which leads to the secretion of autoreactive IgE and to the potential function of these antibodies in AD. Multiple autoantigens have been described to elicit an IgE-dependent response in this context. This IgE autoimmunity starts in infancy and is associated with disease severity. Furthermore, the overall prevalence of autoreactive IgE to multiple auto-antigens is high in AD patients. IgE-antigen complexes can promote a facilitated antigen presentation, a skewing of the adaptive response toward type 2 immunity, and a chronic skin barrier dysfunction and inflammation in patients or AD models. In AD, skin barrier defects and the atopic immune environment facilitate allergen sensitization and the development of other IgE-mediated allergic diseases in a process called the atopic march. AD is also associated epidemiologically with several autoimmune diseases showing autoreactive IgE secretion. Thus, a potential outcome of IgE autoreactivity in AD could be the development of further autoimmune diseases.

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“…Recently, Wang et al observed that acute itch flares were associated with increased serum specific IgE in patients with moderate to severe AD. 4 They showed MC-independent acute itch flares in an AD-like disease murine model sensitized to ovalbumin (OVA) and deficient in MCs (Sash -/mice) upon OVA challenge. Additionally, they performed basophil depletion experiments using anti-CD200R in wild type mice, and diphtheria toxin (DT) in Bas-TRECK mice, which exclusively express the DT receptor on basophils.…”

mentioning

confidence: 99%

“…These data were strengthened by passive immunization experiments with OVA-specific IgE, where acute itch flares were only basophil-dependent in the AD-associated inflammatory disease model. 4 This apparent riddle was explained by the scarce dermis infiltration of circulating basophils without previous inflammation. In contrast, achronically-inflamed environment promoted basophil recruitment that enabled them to migrate through the dermis to interact with sensory neurons.…”

mentioning

confidence: 99%