Antibodies to the amino-terminal domain of desmoglein 1 are retained during transition from pemphigus vulgaris to pemphigus foliaceus

Abstract

Background: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two blistering skin diseases mediated by antibodies to desmoglein 3 (Dsg3) and/or Dsg1. Phenotypic transition from PV to PF is rarely reported. Objectives: To determine the immune response to extracellular (EC) domains of Dsgs during this transition. Materials and Methods: We report two PV patients who subsequently developed a PF phenotype. To map the conformational epitopes in these cases, we examined the reactivity of the sera of two patients by immunoprecipitation-immunoblotting analysis, using five Dsg1/Dsg3 domain-swapped molecules on a backbone of Dsg2. Results: Reactivity exclusively with the EC1 domain of Dsg1 was maintained in both PV and PF stages. No reactivity to Dsg3 in the PF stage was found in patient 1. Various changes in immunoreactivity to Dsg3 were found and the EC1 and EC2 domains of Dsg3 reacted weakly to serum taken at remission and PF stages in patient 2. Conclusions: Our findings suggest that amino-terminal pathogenic antibodies to the EC domain of Dsg1 were retained, while considerable epitope changes occurred in response to Dsg3 during the shift from PV to PF, with an absolute or significant decrease in pathogenic antibodies to the EC1 domain of Dsg3.

Clinical and immunological features of pemphigus relapse

“…The transition from PF to PV is less common than that from PV to PF. In cases experiencing a clinical transition from PV to PF, the change in antibody profile showed two patterns: a shift from anti‐Dsg3 antibodies alone to anti‐Dsg1 antibodies alone, or a shift from both anti‐Dsg1 and anti‐Dsg3 antibodies to anti‐Dsg1 antibodies alone . In contrast, cases with a clinical transition from PF to PV showed the change of antibody profile from anti‐Dsg1 antibodies alone to both anti‐Dsg1 and anti‐Dsg3 or to anti‐Dsg3 antibodies alone .…”

“…This study has demonstrated cases showing a transition of anti‐Dsg antibody profile associated with changes of clinical phenotype at first relapse. Several reports have described the transition of clinical phenotype between PV and PF . The transition from PF to PV is less common than that from PV to PF.…”

Pemphigus

“…In pemphigus vulgaris and pemphigus foliaceus, Nikolsky sign might be positive in the active phase of the disease. A substantial number of patients with pemphigus vulgaris can relapse with a pemphigus foliaceus clinical and histological phenotype, especially when the relapses occur after a long remission 111,112 .…”

Fenômeno de epitope spreading: caracterização clínico imunológica em pacientes portadores de dermatoses bolhosas autoimunes

“…Portanto, o epitope spreading ocorre em pacientes cuja doença progride da forma mucosa para a cutâneo mucosa. Salato et al (26) , (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) .…”

“…Biópsias por punch foram coletadas em área perilesional, e submetidas ao processo descrito a seguir: Tais dados são compatíveis com os relatos da literatura (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) . Esta predominância Komai et al (36) analisaram o soro de 5 pacientes que apresentaram conversão de PV para PF, todos apresentavam valores negativos de Dsg3 no momento da transição, exceto por um que apesar de características clínicas de PF mantinha positividade à Dsg1 e 3.…”