Immunoadsorption in pemphigus

Abstract

The principle of extracorporal immunoadsorption (IA) is based on affinity adsorption of pathogenic (auto-)antibodies and circulating immune complexes (CIC) which reversibly bind to an immobilized ligand of the adsorber. In pemphigus, a blistering autoimmune disease affecting skin and mucous membranes, autoantibodies, mainly of the IgG subclass are directed against desmosomal adhesion molecules and other non-desmosomal antigens on the surface of epidermal keratinocytes, such as acetylcholine receptors. The pathogenicity of these autoantibodies has been shown in various in vitro and in vivo systems. Recently, IA was applied in severe pemphigus demonstrating that a rapid and dramatic decline in desmoglein (Dsg)-reactive autoantibodies is accompanied by clinical remission of mucocutaneous blisters and erosions. As an adjuvant treatment, IA was combined with systemic immunosuppressive medication and current protocols initially apply treatment cycles of 3-4 IAs on consecutive days followed by immunoapheresis once a week or repeating the initial cycle in 4 week intervals depending on the disease activity. IA in pemphigus is generally safe and well tolerated.

Adjuvant rituximab therapy in pemphigus: a single-center experience of 18 cases

“…In this respect, immunosuppressive therapies have been utilized for their steroid-sparing effects, including most commonly mycophenolate mofetil (MMF) and azathioprine (5), although other immunomodulators have been reported such as cyclophosphamide, cyclosporine, methotrexate (MTX) and dapsone (6). Alternative therapies may include intravenous immunoglobulin G (IVIG) where efficacy has been recently confirmed in a prospective, multicenter placebo-controlled trial (7) or immunoadsorption designed to reduce circulating autoantibody levels which appear to correlate with clinical disease activity (8).…”

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

“…IA, the therapeutic removal of IgG autoantibodies, has proven in several autoimmune disorders to be superior to the hitherto mainly employed plasmapheresis which unselectively removes plasma [8,9,10,11]. Recently, numerous case reports and small case series strongly suggest that IA as an adjuvant treatment is highly efficient in removing pathogenic autoantibodies in pemphigus and other autoimmune bullous skin disorders [12].…”

“…Novel therapeutic strategies, such as immunoadsorption (IA) and the B-cell-depleting anti-CD20 antibody rituximab (Rtx), hold great promise to be effective in the remaining refractory, severe cases [7, 8]. …”

Recombinant Human IgA1 and IgA2 Autoantibodies to Type VII Collagen Induce Subepidermal Blistering Ex Vivo

“…With respect to therapy, much effort has been aimed at the development and clinical evaluation of immunoapheresis methods for patients with IgG-mediated blistering diseases of the skin (59)(60)(61). Despite its nonselectivity, the removal of IgG from patient plasma by protein A immunoapheresis is successful at reducing disease activity.…”