Inhibition of Neutrophil Adherence to Antibody by Daspone: A Possible Therapeutic Mechanism of Dapsone in the Treatment of IgA Dermatoses

Nguyen, Vu Thuong; Kadunce, Donald P.; Hendrix, John D.; Gammon, W. Ray; Zone, John J.

doi:10.1111/1523-1747.ep12471811

Cited by 84 publications

(29 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One proposed mechanism is that dapsone inhibits the neutrophil recruitment to IgA and IgG antibodies attached to the basement membrane zone in a dose-dependent manner by blocking the interaction between the Fc portions of these antibodies and the circulating neutrophils [35] . Several other mechanisms regarding dapsone's anti-inflammatory properties have been previously proposed.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Baum¹,

Debby²,

Gilboa³

et al. 2016

Dermatology

View full text Add to dashboard Cite

Background: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease. Most patients require long-term therapy with systemic steroids, and a steroid-sparing agent is usually also utilized. Dapsone is a chemotherapeutic agent with anti-inflammatory properties that is used as a steroid-sparing agent in PV. Objective: The aim of the present study was to evaluate the efficacy of dapsone as an adjuvant therapy in patients with PV. Methods: A retrospective analysis of patients' files was performed. All 26 patients included in the study group were treated with dapsone as an adjuvant to systemic steroids for at least 3 consecutive months and were followed up during their dapsone treatment period. Results: After 3 months of treatment with dapsone, 13 patients were in the consolidation phase, 4 patients demonstrated partial remission on minimal therapy, 7 patients demonstrated complete remission on minimal therapy, and 2 patients were defined as treatment failures. The trend of clinical improvement continued after 6 months of treatment and at the study end point. Conclusion: This retrospective case series, one of the largest reported, indicates that dapsone is efficacious and safe for patients with PV in whom it is well tolerated soon after the initiation of treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Baum¹,

Debby²,

Gilboa³

et al. 2016

Dermatology

View full text Add to dashboard Cite

show abstract

“…99 In skin section assays, therapeutic dapsone levels inhibited neutrophils' adhesion to epidermis 93 or basement membrane bound antibody. 91 Dapsone thus inhibits neutrophil accretions, migration, and response to IL-8, and production of IL-8-all potentially useful attributes in treating GB. Repression of endogenous IL-8 production in GB cells or addition of IL-8 neutralizing antibodies reduce GB proliferation and invasion.…”

Section: Dapsonementioning

confidence: 99%

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

Kast¹,

Hill

Wion

et al. 2017

Tumour Biol.

View full text Add to dashboard Cite

Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain-be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation-increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration-and European Medicines Agency-approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.

show abstract

“…Dapsone has also been shown to inhibit F-met-leu-phe-derived chemotaxis, but not to inhibit chemotaxis to C5a. We evaluated the role of dapsone in the neutrophil attachment assay and found that it inhibits the adherence of neutrophils to basement membrane zone antibody in a dose-dependent manner that covers the pharmacologic range of serum dapsone levels (Thuong-Nguyen et al, 1993). Nevertheless, this still does not explain how dapsone inhibits chemotaxis of neutrophils into sites of IgA deposition.…”

Section: Dermatitis Herpetiformismentioning

confidence: 99%

IgA Autoimmune Disorders: Development of a Passive Transfer Mouse Model

Zone

Egan

Taylor

et al. 2004

Journal of Investigative Dermatology Symposium Proceedings

Self Cite

View full text Add to dashboard Cite

IgA is present in the skin in several dermatoses, including dermatitis herpetiformis, linear IgA bullous dermatosis, and Henoch-Schoenlein purpura. The neutrophilic infiltration in the area of the IgA deposition suggests that IgA is responsible for the associated inflammatory events. The mechanism for this process is unproven, but is likely to involve IgA-mediated neutrophil chemotaxis with inhibition of chemotaxis by dapsone. Elucidation of the mechanism of IgA-mediated inflammation will require an animal model. We have established a model for linear IgA bullous dermatosis as a prototype disease to be studied. IgA mouse monoclonal antibodies against a linear IgA bullous dermatosis antigen have been passively transferred to SCID mice with human skin grafts. This has produced neutrophil infiltration and basement membrane vesiculation in 4 of 12 mice tested. We conclude that an animal model for the pathogenesis of IgA dermatoses with IgA deposition and inflammation can be produced by passive transfer of mouse IgA antibodies against a linear IgA antigen.

show abstract

Inhibition of Neutrophil Adherence to Antibody by Daspone: A Possible Therapeutic Mechanism of Dapsone in the Treatment of IgA Dermatoses

Cited by 84 publications

References 39 publications

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

IgA Autoimmune Disorders: Development of a Passive Transfer Mouse Model

Contact Info

Product

Resources

About