Treatment of epidermolysis bullosa acquisita with the humanized anti-Tac mAb daclizumab

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease characterized by IgG anti-basement membrane autoantibodies to collagen VII. Since autoantibody formation in EBA patients is thought to be T-cell-dependent, the degree of T cell activation in three patients (all ma...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 101(2001), 2 vom: 01. Nov., Seite 146-51
1. Verfasser: Egan, C A (VerfasserIn)
Weitere Verfasser: Brown, M, White, J D, Yancey, K B
Format: Aufsatz
Sprache:English
Veröffentlicht: 2001
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, U.S. Gov't, P.H.S. Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Epitopes Immunoglobulin G Immunosuppressive Agents Receptors, Interleukin-2 Daclizumab CUJ2MVI71Y
Beschreibung
Zusammenfassung:Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease characterized by IgG anti-basement membrane autoantibodies to collagen VII. Since autoantibody formation in EBA patients is thought to be T-cell-dependent, the degree of T cell activation in three patients (all males, ages 33-44 years) was assessed by quantitation of soluble Tac, a fragment of the alpha-subunit of the high-affinity IL-2 receptor (CD25). Soluble Tac levels in all patients were elevated [highest random values, 2430, 920, and 560 IU/ml (normal range, 112-502)]. Based on such findings, these patients were treated with the humanized murine monoclonal anti-Tac antibody daclizumab (1 mg/kg, 6-12 iv treatments at 2- to 4-week intervals). All patients had a significant, rapid, and persistent decrease in lymphocyte CD25 expression. Though a moderate decrease in lymphocyte expression of 7G7, an IL-2 receptor epitope not bound by daclizumab, was noted, stable levels of CD3 cells and in vitro saturation studies indicated that daclizumab effectively bound CD25 and did not promote clearance of such cells from peripheral blood. There were no complications and no patient developed antibodies against daclizumab. While no apparent clinical benefit was seen in two patients with dermolytic disease, one patient with inflammatory EBA had a favorable response. While on daclizumab, this patient stopped prednisone, significantly reduced dapsone, and improved clinically. Furthermore, his disease flared when treatment was stopped, and resumption of daclizumab again effected improvement within 2 weeks. Daclizumab therapy is safe and well tolerated in EBA patients. It may be effective as a corticosteroid sparing agent in patients with inflammatory EBA
Beschreibung:Date Completed 07.12.2001
Date Revised 30.11.2018
published: Print
Citation Status MEDLINE
ISSN:1521-7035