Prolonged Clinical Remission of Patients with Severe Pemphigus upon Rapid Removal of Desmoglein-Reactive Autoantibodies by Immunoadsorption

Abstract

Background: In pemphigus, loss of epidermal adhesion is induced by binding of circulating autoantibodies to the desmosomal cadherins desmoglein 3 (Dsg3) in pemphigus vulgaris (PV) and desmoglein 1 (Dsg1) in pemphigus foliaceus (PF), respectively. Therapeutic removal of Dsg-reactive autoantibodies by immunoadsorption (IA) has been demonstrated to exert clinical remission of the disease. Objectives: The aim of this intervention study was to evaluate the efficacy and safety of the peptide-based Globaffin^® adsorber system in the treatment of severe pemphigus cases. Patients and Methods: We applied IA in 4 PV and 2 PF patients with severe chronic disease resistant to conventional immunosuppressive therapy. IA was performed on 4 consecutive days, representing 1 treatment cycle, followed by a 4-week treatment-free interval. Serum samples for determining serum IgG and anti-Dsg1/Dsg3 IgG autoantibodies were drawn daily before and after IA, respectively. During follow-up, patients were examined carefully, and laboratory parameters were controlled monthly for up to 1 year. Results: IA led to excellent clinical responses. Skin and mucosal lesions cleared almost completely within weeks. One IA cycle reduced anti-Dsg1 and anti-Dsg3 autoantibodies by an average of 50–70% as determined by ELISA. Conclusions: Using the Globaffin adsorber system, IA represents an effective and safe treatment opportunity in severe and therapy-resistant pemphigus.

Clinical and Immunological Follow-Up of Pemphigus Patients on Adjuvant Treatment with Immunoadsorption or Rituximab

“…IA with the Globaffin adsorber system effectively reduced Dsg1/3-reactive IgG by an average of 50–70% per IA cycle accompanied by a rapid clinical improvement of cutaneous and mucosal lesions within 4–8 weeks. Within a follow-up period of up to 2 years, 3 patients still remained in complete remission on minimal therapy and 3 patients showed clinical relapses with residual cutaneous and mucosal erosions [19]. As previously shown by Amagai et al [23], IA with columns that were coated with recombinant Dsg3 effectively reduced pathogenic IgG in a passive transfer mouse model of pemphigus.…”

“…Based on a recent study, showing that IA led to a rapid decrease in anti-Dsg1 and anti-Dsg3 autoantibodies [19], IA was administered in PV patients with high serum autoantibody titers. Treatment with IA reduced IgG titers against Dsg1 and Dsg3 faster than Rtx.…”

“…In our experience, IA with an adsorber column containing the PGAM146 peptide (Globaffin®, Fresenius Medical Care) led to fast and prolonged clinical remission in 4 PV and 2 PF patients with long-standing, extensive disease which was refractory despite high-dose immunosuppressive therapy consisting of glucocorticoids (1–2 mg prednisolone/kg/day) and immunosuppressive adjuvant drugs [19]. IA was performed on 4 consecutive days followed by a second cycle of 4 subsequent IA treatments 4 weeks later and monthly intravenous pulses with cyclophosphamide as an immunosuppressive adjuvant.…”

Linear IgA Disease: Successful Application of Immunoadsorption and Review of the Literature

“…Bullous diseases so far treated with IA had all been IgG mediated and mainly included pemphigus and a few patients with bullous pemphigoid, pemphigoid gestationis and epidermolysis bullosa acquisita [3,4,5,6,7]. Advantages of IA compared to plasmapheresis comprise the more specific reduction of immunoglobulin levels, the processing of larger plasma volumes and the avoidance of substitution with foreign proteins [7].…”

“…Immunoadsorption (IA) allows the rapid reduction of circulating autoantibodies. Following its successful adjuvant application in treatment-refractory pemphigus [3,4,5,6], IA has been increasingly used for various other IgG-mediated severe and/or treatment-resistant autoimmune bullous diseases including bullous pemphigoid, pemphigoid gestationis and epidermolysis bullosa acquisita [5,7]. However, IA has not been applied in IgA-mediated blistering autoimmune diseases so far.…”