Immunofluorescent determination of the isotype of serum antikeratinocyte autoantibodies in dogs with Pemphigus foliaceus

Abstract

In humans with pemphigus foliaceus (PF), pathogenic autoantibodies are suspected to be of IgG4 subclass. The goals of this study were to determine the isotypes of circulating autoantibodies in dogs with PF, and to assess whether serum autoantibody titers decreased during successful treatment outcome. Using an indirect immunofluorescence assay performed on neonatal mouse skin sections, circulating IgG autoantibodies were detected in 36 out of 44 dogs with PF (82%). Serum autoantibodies belonged predominantly to IgG4 (35/44; 80%) and IgG1 (30/44; 68%) subclasses. Circulating IgA and IgE autoantibodies were not found. Serum IgG autoantibodies targeted autoantigens in both superficial and/or basal epidermal layers. Remarkably, antikeratinocyte IgG autoantibodies were detected in 16 out of 20 normal dogs (80%), and these autoantibodies were of IgG1 (16/20, 80%) but rarely of IgG4 (2/20; 10%) isotypes. Antikeratinocyte IgG, IgG1 and IgG4 autoantibody serum titers were followed in six dogs with PF while the severity of their clinical signs decreased with immunosuppression. IgG, IgG1 and IgG4 autoantibody serum titers decreased during remission in four (67%), one (17%) and four (67%) dogs, respectively. Conversely, serum IgG, IgG1 and IgG4 autoantibody titers increased during remission in one (17%), one (17%) and no dogs, respectively. These observations suggest that, in dogs with PF, antikeratinocyte IgG4 autoantibodies could be relevant to the pathogenesis of the disease and that monitoring of IgG4 autoantibody titers could be useful for assessment of clinical outcome. Remarkably, the detection of circulating IgG1 antikeratinocyte autoantibodies in normal dogs is similar to the situation observed in geographical areas where human PF is endemic.