Serum and blister fluid levels of cytokines and chemokines in pemphigus and bullous pemphigoid

Kowalski, Eric H.; Kneibner, Diana; Kridin, Khalaf; Amber, Kyle T.

doi:10.1016/j.autrev.2019.03.009

Cited by 78 publications

(59 citation statements)

References 173 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Autoreactive Th2 cells are thought to exert a dual role in BP: they stimulate proliferation and autoantibody production by B-cells via CD40-CD40L interaction and contribute to eosinophil recruitment and activation. Of note, IL-4 as well as IL-5 was found to be higher in blister fluid than in serum, suggesting a lesional gradient (Kowalski, Kneibner, Kridin, & Amber, 2019). Furthermore, Büdinger et al (1998) demonstrated a type-2 response to BP180 in BP patients, in opposition to MHCII restricted controls who mounted a type-1 response without disease.…”

Section: Bullous Pemphigoidmentioning

confidence: 91%

“…Furthermore, Büdinger et al (1998) demonstrated a type-2 response to BP180 in BP patients, in opposition to MHCII restricted controls who mounted a type-1 response without disease. Of note, IL-4 as well as IL-5 was found to be higher in blister fluid than in serum, suggesting a lesional gradient (Kowalski, Kneibner, Kridin, & Amber, 2019). Teraki, Hotta, and Shiohara (2001) investigated the frequencies of IL-4 and IL-13 producing T-cells and their correlation with the expression of skin-homing receptors (cutaneous lymphocyteassociated antigen) in peripheral blood and skin blisters of patients with BP.…”

Section: Bullous Pemphigoidmentioning

confidence: 99%

See 1 more Smart Citation

Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

Russo

Cozzani

Gasparini

et al. 2020

Dermatologic Therapy

View full text Add to dashboard Cite

Bullous pemphigoid, mucous membrane pemphigoid, and pemphigus vulgaris are different cutaneous autoimmune blistering diseases, with complex pathogenic mechanisms. In all of them, a type-2 response is thought to have a central role. Interleukin 4 and Interleukin 13 are crucial cytokines in type-2 response. Treatment of these conditions is often challenging. Dupilumab, a recombinant fully human IgG4 monoclonal antibody with binding specificity to human interleukin-4 receptor IL-4Rα, has the potential to inhibit both IL-4 and IL-13. We propose IL-4Rα as a theoretical drug target for cutaneous autoimmune bullous diseases. K E Y W O R D Sblistering diseases, bullous pemphigoid, dupilumab, mucous membrane pemphigoid, pemphigus vulgaris

show abstract

Section: Bullous Pemphigoidmentioning

confidence: 91%

Section: Bullous Pemphigoidmentioning

confidence: 99%

Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

Russo

Cozzani

Gasparini

et al. 2020

Dermatologic Therapy

View full text Add to dashboard Cite

show abstract

“…Evidence supports an association between RA and IL-17 elucidating that excessive IL-17 receptor signaling is an essential pathway in converting an acute synovitis into the chronically damaging arthritis seen in RA [26][27][28]. Likewise, a recent meta-analysis has identified vastly increased levels of serum IL-17 in patients with pemphigus, perhaps expounding on the association between pemphigus and RA [29].…”

Section: Putative Interpretation For the Study Findingsmentioning

confidence: 99%

Patients with pemphigus are at an increased risk of developing rheumatoid arthritis: a large-scale cohort study

et al. 2020

Self Cite

View full text Add to dashboard Cite

Data regarding the association between pemphigus and rheumatoid arthritis (RA) is inconclusive and yet to be firmly established. In the current study, we aimed to evaluate the risk of developing RA during the course of pemphigus. A large-scale population-based longitudinal cohort study was conducted to evaluate the hazard ratio (HR) of RA among 1985 patients with pemphigus relative to 9874 age-, sex-, and ethnicity-matched control subjects. A multivariate Cox regression model was utilized. The incidence of RA was 1.07 (95% CI, 0.62–1.72) and 0.36 (95% CI, 0.24–0.52) per 1000 person-years among patients with pemphigus and controls, respectively. The lifetime prevalence of RA was 2.3% (95% CI, 1.7–3.1%) among cases and 1.8% (95% CI, 1.5–2.0%) among controls. Patients with pemphigus were more than twice as likely to develop RA as compared to control subjects (adjusted HR, 2.54; 95% confidence interval [CI], 1.31–4.92). The increased risk was robust to a sensitivity analysis that included only cases managed by pemphigus-related systemic medications (adjusted HR, 2.56; 95% CI, 1.30–5.05). In conclusion, pemphigus is associated with an increased risk of RA. Physicians treating patients with pemphigus should be aware of this possible association. Further research is required to better understand the mechanism underlying this association.

show abstract

“…Additionally, IL‐5 modulates differentiation, survival and degranulation of eosinophils and is significantly elevated peripherally, and lesionally in BP . Akin to eotaxin‐1, a serum to lesional gradient is present for IL‐5 that together may explain the highly localized and destructive cellular infiltrates formed in BP . Immunotherapies directed at neutralizing IL‐5 have been trialed in several hypereosinophilic diseases, and mepolizumab, an anti‐IL5 antibody, is currently FDA approved for asthma and eosinophilic granulomatosis with polyangiitis .…”

Section: Evolving Therapeutic Targetsmentioning

confidence: 99%

“…182,183 Akin to eotaxin-1, a serum to lesional gradient is present for IL-5 that together may explain the highly localized and destructive cellular infiltrates formed in BP. 184,185 Immunotherapies directed at neutralizing IL-5 have been trialed in several hypereosinophilic diseases, and mepolizumab, an anti-IL5 antibody, is currently FDA approved for asthma and eosinophilic granulomatosis with polyangiitis. [186][187][188] Its efficacy in BP is currently under investigation in a phase II, randomized, placebo-controlled, double-blind study (NCT01705795).…”

Section: Epidermolysis Bullosa Acquisitamentioning

confidence: 99%

From bench to bedside: evolving therapeutic targets in autoimmune blistering disease

Kridin

Kowalski

Kneiber

et al. 2019

Acad Dermatol Venereol

View full text Add to dashboard Cite

Autoimmune blistering diseases comprise a group of heterogenous conditions characterized by the loss of tolerance and subsequent development of autoantibodies targeting epidermal and subepidermal adhesion proteins. Blisters and erosions form on the skin and mucous membranes leading to significant morbidity and mortality. Traditional therapies rely on systemic immunosuppression. Advancements in our understanding of the pathophysiology of pemphigus and pemphigoid have led to the development of molecules which target specific pathways involved in induction and perpetuation of disease. In this review, we outline the novel therapeutic strategies including B‐cell depletion, T‐regulatory cell repletion, cell signalling inhibitors and small molecular inhibitors, inhibitory monoclonal antibodies, as well as complement inhibition. We additionally review their current level of clinical evidence. We lastly review therapeutics targets gleaned from the experimental epidermolysis bullosa acquisita mouse model. These emerging treatments offer an exciting progression from basic science discoveries that have the potential to transform the treatment paradigm in autoimmune blistering diseases.

show abstract

Serum and blister fluid levels of cytokines and chemokines in pemphigus and bullous pemphigoid

Cited by 78 publications

References 173 publications

Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

Patients with pemphigus are at an increased risk of developing rheumatoid arthritis: a large-scale cohort study

From bench to bedside: evolving therapeutic targets in autoimmune blistering disease

Contact Info

Product

Resources

About