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

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blister ing disease characterized by IgG anti-basement membrane autoantibodies to c ollagen 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 les, ages 33-44 years) was assessed by quantitation of soluble Tac, a fragm ent of the a-subunit of the high-affinity IL-2 receptor (CD25). Soluble Tac levels in all patients were elevated [highest random values, 2430, 920, an d 560 IU/ml (normal range, 112-502)] Based on such findings, these patients were treated with the humanized murine monoclonal anti-Tac antibody dacliz umab (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 expres sion. Though a moderate decrease in lymphocyte expression of 7G7, an IL-2 r eceptor epitope not bound by daclizumab, was noted, stable levels of CD3 ce lls and in vitro saturation studies indicated that daclizumab effectively b ound CD25 and did not promote clearance of such cells from peripheral blood . There were no complications and no patient developed antibodies against d aclizumab. While no apparent clinical benefit was seen in two patients with dermolytic disease, one patient with inflammatory EBA had a favorable resp onse. While on daclizumab, this patient stopped prednisone, significantly r educed dapsone, and improved clinically. Furthermore, his disease flared wh en treatment was stopped, and resumption of daclizumab again effected impro vement within 2 weeks. Daclizumab therapy is safe and well tolerated in EBA patients. It may be effective as a corticosteroid sparing agent in patient s with inflammatory EBA.