Bullous pemphigoid: The role of type 2 inflammation in its pathogenesis and the prospect of targeted therapy

Zhang, Luyao; Chen, Zihua; Wang, Lanting; Luo, Xiaoqun

doi:10.3389/fimmu.2023.1115083

Cited by 10 publications

(6 citation statements)

References 146 publications

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“…Previous studies [7][8] have pointed out that uncontrolled systemic inflammatory response is a characteristic of early sepsis. The levels of inflammatory factors in the plasma of sepsis patients significantly increase, with an increase in monocyte chemotactic protein-1 levels indicating the migration of a large number of immune cells from the bone marrow, and an increase in IL-1β levels indicating the activation of inflammatory bodies [9].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Panx1 reduces neuroinflammatory response and alleviates brain damage in septic mice

Lei

2024

TMBLS

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Objective: This study mainly investigates whether Pannexin 1 protein (i.e. Panx1) plays a role in the progression of brain injury in sepsis mice and its potential mechanisms. Methods: A total of 45 clean grade adult male C57BL/6 healthy mice were selected and divided into three groups using a random number table method, namely the sham group, the cecal ligation perforation (CLP) group, and the CBX pretreatment plus cecal ligation perforation (CBX+CLP) group, with 15 mice in each group. Excluding the Sham group, the remaining two groups of study mice were used to prepare sepsis brain injury models using the CLP method. The CBX+CLP group was injected into the lateral ventricles of both sides of the mouse half an hour before the modeling process, with a total amount of 1 μL CBX, which was injected into the bilateral lateral ventricles of the other two groups of mice with the same dose of physiological saline solution. 24 hours after the completion of modeling, three groups of mice were evaluated for neurological behavior. Subsequently, all mice were euthanized. After the cardiac perfusion phase, brain tissue of the mice was taken to observe the pathological damage of the hippocampal tissue. The effective content of IL-1β and TNF‐α in the mouse's hippocampal tissue was measured, and the expression of Panx1 protein, Caspase-1, NLRP3 protein, as well as NLRP3, Panx1, Caspase-1, TNF‐α, IL-1β were measured the mRNA of corresponds to its expression status. Results: Compared with Sham group mice, the neurobehavioral score of CLP group mice significantly decreased, and the pathological damage degree of hippocampal neurons in mice was significant. The expression levels of inflammatory factors IL-1β and TNF‐α were increased, and the corresponding expression levels of Panx1, NLRP3, Caspase-1 proteins and mRNA were increased. The mRNA expression levels of inflammatory factors IL-1β and TNF were also increased (P<0 05), compared to the CLP group mice, the CBX+CLP group mice showed an increase in neurobehavioral scores, a reduction in pathological damage to hippocampal tissue, a decrease in the expression of inflammatory factors IL-1β and TNF‐α, a decrease in the expression levels of NLRP3, Panx1, Caspase-1 proteins, and corresponding mRNA, and a corresponding decrease in the mRNA expression of the two inflammatory factors (P<0 05). Conclusion: Inhibiting Panx1 can reduce the degree of neural inflammatory response, thereby improving brain damage in sepsis mice, which may be related to the limited activation of NLRP3 inflammasomes.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Panx1 reduces neuroinflammatory response and alleviates brain damage in septic mice

Lei

2024

TMBLS

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“… 51 , 52 , 53 It is believed that type 2 inflammation triggers the formation of autoantibodies in BP. 54 The levels of interleukin (IL)‐4, IL‐5, and IL‐13 were reportedly elevated in the serum, blister fluid, and skin biopsy specimens among patients with BP. 55 These cytokines may also involve the pathogenesis of VTE.…”

Section: Discussionmentioning

confidence: 99%

Risk of Incident Venous Thromboembolism Among Patients With Bullous Pemphigoid or Pemphigus Vulgaris: A Nationwide Cohort Study With Meta‐Analysis

Chen,

Huang,

Loh

et al. 2023

JAHA

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Background Bullous pemphigoid (BP) and pemphigus vulgaris (PV) share similar pathophysiology with venous thromboembolism (VTE) involving platelet activation, immune dysregulation, and systemic inflammation. Nevertheless, their associations have not been well established. Methods and Results To examine the risk of incident VTE among patients with BP or PV, we performed a nationwide cohort study using Taiwan's National Health Insurance Research Database and enrolled 12 162 adults with BP or PV and 12 162 controls. A Cox regression model considering stabilized inverse probability weighting was used to calculate the hazard ratios (HRs) for incident VTE associated with BP or PV. To consolidate the findings, a meta‐analysis that incorporated results from the present cohort study with previous literature was also conducted. Compared with controls, patients with BP or PV had an increased risk for incident VTE (HR, 1.87 [95% CI, 1.55–2.26]; P <0.001). The incidence of VTE was 6.47 and 2.20 per 1000 person‐years in the BP and PV cohorts, respectively. The risk for incident VTE significantly increased among patients with BP (HR, 1.85 [95% CI, 1.52–2.24]; P <0.001) and PV (HR, 1.99 [95% CI, 1.02–3.91]; P =0.04). In the meta‐analysis of 8 studies including ours, BP and PV were associated with an increased risk for incident VTE (pooled relative risk, 2.17 [95% CI, 1.82–2.62]; P <0.001). Conclusions BP and PV are associated with an increased risk for VTE. Preventive approaches and cardiovascular evaluation should be considered particularly for patients with BP or PV with concomitant risk factors such as hospitalization or immobilization.

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“…Consequently, it might be considered a potential additional medication for controlling pruritus in BP in the future. However, no clinical trials have been planned thus far [ 22 ].…”

Section: Therapymentioning

confidence: 99%

“…Anti-BP180 IgG can be found in 95% of patients with BP, while anti-BP230 is detected in 70% of patients with BP [ 21 ]. The incidence of anti-BP180 IgE varies widely among patients [ 22 ]. Anti-BP180 IgE can bind to FcεRI receptors in mast cells, leading to a crosslink with hemidesmosomal BP180 in the DEJ, degranulation of mast cells, and histamine release, amplifying the chemotaxis of eosinophils and neutrophils (Fig.…”

Section: Introductionmentioning

confidence: 99%

Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update

Karakioulaki,

Eyerich,

Patsatsi

2023

Am J Clin Dermatol

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Abastract Bullous pemphigoid (BP) is a common autoimmune bullous disease affecting mainly the elderly, with rising incidence due to increased life expectancy. This disease is characterized by tense bullous lesions on normal or erythematous skin, accompanied by pruritus. BP pathogenesis involves autoantibodies against hemidesmosomal proteins BP180 and BP230, leading to detachment at the dermo-epidermal junction as well as blister formation. BP is associated with coexisting comorbidities and drug exposure, and its management often requires high doses or chronic use of systemic glucocorticoids, posing risks of adverse effects. This review focuses on novel treatment options for BP, exploring therapies targeting different immune pathways. Rituximab, a CD20 monoclonal antibody, depletes B-lymphocytes and has shown efficacy in severe cases. Dupilumab, targeting interleukin (IL)-4 receptor α and thus blocking IL-4 and IL-13, downregulates type 2 helper (Th2) responses and has demonstrated promising results. Targeting eosinophil-related molecules using bertilimumab and AKST4290 has yielded positive results in clinical trials. Omalizumab, an immunoglobulin (Ig) E antibody, can reduce disease severity and allows corticosteroid tapering in a number of cases. Complement inhibitors such as nomacopan and avdoralimab are being investigated. IL-17 and IL-23 inhibitors such as secukinumab and tildrakizumab have shown potential in a limited number of case reports. Neonatal Fc receptor antagonists such as efgartigimod are under investigation. Additionally, topical therapies and Janus kinase inhibitors are being explored as potential treatments for BP. These novel therapies offer promising alternatives for managing BP, with potential to improve outcomes and reduce high cumulative doses of systemic corticosteroids and related toxicities. Further research, including controlled clinical trials, is needed to establish their efficacy, safety, and optimal dosing regimens for BP management.

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Bullous pemphigoid: The role of type 2 inflammation in its pathogenesis and the prospect of targeted therapy

Cited by 10 publications

References 146 publications

Inhibition of Panx1 reduces neuroinflammatory response and alleviates brain damage in septic mice

Inhibition of Panx1 reduces neuroinflammatory response and alleviates brain damage in septic mice

Risk of Incident Venous Thromboembolism Among Patients With Bullous Pemphigoid or Pemphigus Vulgaris: A Nationwide Cohort Study With Meta‐Analysis

Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update

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