Treatment of Pemphigus Vulgaris

Yeh, Shih Wei; Sami, Naveed; Ahmed, Razzaque A.

doi:10.2165/00128071-200506050-00006

Cited by 73 publications

(17 citation statements)

References 146 publications

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“…The use of B-cell depleting agents have proven particularly effective for PV, although these approaches can cause undesirable side effects (Yeh et al , 2005; Zakka et al , 2012). Therefore, recent efforts in the field have sought to find approaches that render the skin resistant to an ongoing autoimmune response.…”

Section: Discussionmentioning

confidence: 99%

Plakophilin-1 Protects Keratinocytes from Pemphigus Vulgaris IgG by Forming Calcium-Independent Desmosomes

Tucker

Stahley

Kowalczyk

2014

Journal of Investigative Dermatology

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Plakophilin-1 (PKP-1) is an armadillo family protein critical for desmosomal adhesion and epidermal integrity. In the autoimmune skin blistering disease pemphigus vulgaris (PV), autoantibodies (IgG) target the desmosomal cadherin desmoglein 3 (Dsg3) and compromise keratinocyte cell-cell adhesion. Here, we report that enhanced expression of PKP-1 protects keratinocytes from PV IgG-induced loss of cell-cell adhesion. PKP-1 prevents loss of Dsg3 and other desmosomal proteins from cell-cell borders and prevents alterations in desmosome ultrastructure in keratinocytes treated with PV IgG. Using a series of Dsg3 chimeras and deletion constructs, we find that PKP-1 clusters Dsg3 with the desmosomal plaque protein desmoplakin in a manner dependent upon the plakoglobin binding domain of the Dsg3 tail. Furthermore, PKP-1 expression transforms desmosome adhesion from a calcium-dependent to a calcium-independent and hyper-adhesive state. These results demonstrate that manipulating the expression of a single desmosomal plaque protein can block the pathogenic effects of PV IgG on keratinocyte adhesion.

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Section: Discussionmentioning

confidence: 99%

Plakophilin-1 Protects Keratinocytes from Pemphigus Vulgaris IgG by Forming Calcium-Independent Desmosomes

Tucker

Stahley

Kowalczyk

2014

Journal of Investigative Dermatology

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“…The overall incidence rate of PV ranges from 0.1 to 3.2 cases per100,000 inhabitants/year [1], and it seems to be more frequently reported in Ashkenazi Jews than in individuals from other ethnic groups [2]. Histologically, the disease is characterized primarily by the presence of IgG4 antibodies against desmoglein-3, a cadherin-like transmembrane glycoprotein that mediates cell-cell adhesion in keratinocytes of the epidermis and mucous membranes.…”

Section: Introductionmentioning

confidence: 99%

Th1/Th17-Related Cytokines and Chemokines and Their Implications in the Pathogenesis of Pemphigus Vulgaris

Timóteo

Silva

Miguel

et al. 2017

Mediators of Inflammation

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Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-3. Despite the variety of findings, the chemokine and cytokine profiles that characterize the immune response in the disease are still poorly explored. Thus, 20 PV patients and 20 controls were grouped according to gender, ethnicity, place of residence, and clinical parameters of the disease. Then, the levels of chemokines and of Th1/Th2/Th17/Treg/Th9/Th22-related cytokines were assessed in the serum. PV patients had higher levels of inflammatory Th1/Th17 cytokines (IFN-γ, IL-17, and IL-23), as well as higher levels of CXCL8 and reduced levels of Th1/Th2-related chemokines (IP-10 and CCL11). However, no differences in the levels of IL-2, IL-6, TNF-α, IL-1β, IL-4, IL-9, IL-12, TGF-β, IL-33, MCP-1, RANTES, and MIP-1α were found between PV patients and their control counterparts. Furthermore, PV patients with skin lesions had higher serum levels of IL-6 and CXCL8 when compared to PV patients without lesions. Taken together, our findings describe the role of cytokines and chemokines associated with Th1/Th17 immune response in PV patients. Finally, these data are important for better understanding of the immune aspects that control disease outcome, and they may also provide important information about why patients develop autoantibodies against desmogleins.

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“…The advent of corticosteroids has improved prognosis, and the current mortality is estimated to be 5-10% [3]. Combination with other immunosuppressants, such as azathioprine, methotrexate, mycophenolate mofetil, cyclophosphamide and cyclosporine, allows for a steroid-sparing effect.…”

Section: Introductionmentioning

confidence: 99%

Pilot Study of 19 Patients with Severe Pemphigus: Prophylactic Treatment with Rituximab Does Not Appear to be Beneficial

Gregoriou

Giatrakou²,

Θεοδωρόπουλος³

et al. 2014

Dermatology

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Aims: To assess the efficacy and safety of rituximab in refractory pemphigus and the possible benefit of an additional prophylactic infusion at 6 months. Methods: Seventeen patients with pemphigus vulgaris, 1 with pemphigus foliaceus and 1 with pemphigus vegetans were treated with 4 weekly infusions of rituximab (375 mg/m²). Nine patients received an additional prophylactic infusion after 6 months while the rest received no maintenance therapy. In case of recurrence, an additional single infusion was administered. Results: Control of the disease was obtained after 3-8 weeks. End of the consolidation phase for all patients was observed after 16 weeks. Patients remained in full remission for 7-42 months. All immunosuppressive agents, including prednisone, were discontinued after 2-12 months. The disease relapsed in 5 out of 9 patients who received the additional prophylactic infusion, and in 3 out of 10 patients among those skipping the prophylactic additional infusion. Conclusion: One course of rituximab and treatment of relapses is highly effective and well tolerated in the treatment of refractory pemphigus. In this pilot study of 19 patients, the prophylactic infusion does not appear to have provided any additional benefit to the patients receiving it.

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Treatment of Pemphigus Vulgaris

Cited by 73 publications

References 146 publications

Plakophilin-1 Protects Keratinocytes from Pemphigus Vulgaris IgG by Forming Calcium-Independent Desmosomes

Plakophilin-1 Protects Keratinocytes from Pemphigus Vulgaris IgG by Forming Calcium-Independent Desmosomes

Th1/Th17-Related Cytokines and Chemokines and Their Implications in the Pathogenesis of Pemphigus Vulgaris

Pilot Study of 19 Patients with Severe Pemphigus: Prophylactic Treatment with Rituximab Does Not Appear to be Beneficial

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