title: The pathogenic activity of anti-desmoglein autoantibodies parallels disease severity in rituximab-treated patients with pemphigus vulgaris.
abstract: BACKGROUND
  Pemphigus vulgaris (PV) is an autoimmune blistering disease mediated by IgG autoantibodies targeting desmogleins (Dsgs). The anti-CD20 monoclonal antibody rituximab is increasingly used in corticosteroid-resistant PV patients. In a subset of rituximab-treated patients in remission, high ELISA index values have been reported; however, their significance remains so far unclear.
  
  
  OBJECTIVE
  To address the discrepancy between anti-Dsg3 serum antibody titers and disease severity.
  
  
  METHODS
  6 rituximab-treated PV patients were prospectively followed-up for two years and anti-Dsg3 autoantibodies levels and pathogenic activity were measured.
  
  
  RESULTS
  All patients achieved complete remission without any serious side effects. Both anti-Dsg3 autoantibodies (p = 0.031) and their pathogenic activity (p = 0.003) were significantly related to disease severity. However, in selected patients, the dissociation index was a more sensitive indicator for PV clinical activity than the ELISA index.
  
  
  CONCLUSIONS
  Our findings have demonstrated the existence of non-pathogenic autoantibodies in PV patients in remission, establishing the basis for the design of a system able to precisely monitor the course of disease.
authors.affiliation: Molecular and Cell Biology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), 00167 Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sinistro
authors.affiliation: Molecular and Cell Biology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), 00167 Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Calabresi
authors.affiliation: V Dermatology Division, IDI-IRCCS, 00167 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lupi
authors.affiliation: Lifecourse Epidemiology and Biostatistics, Population, Policy and Practise, UCL Institute of Child health, London, WC1N 1EH, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sera
authors.affiliation: Immunology and Allergology Laboratory, IDI-IRCCS, 00167 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Frezzolini
authors.affiliation: Immunology and Allergology Laboratory, IDI-IRCCS, 00167 Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Ruffelli
authors.affiliation: Immunology and Allergology Laboratory, IDI-IRCCS, 00167 Rome, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: De Pità
authors.affiliation: Molecular and Cell Biology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), 00167 Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Camaioni
authors.affiliation: V Dermatology Division, IDI-IRCCS, 00167 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cianchini
authors.affiliation: Molecular and Cell Biology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), 00167 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Zenzo
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D051182:Desmogleins / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008856:Microscopy, Fluorescence; D010392:Pemphigus / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012074:Remission Induction; D000069283:Rituximab / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D051182:Desmogleins; D000069283:Rituximab
keywords: ELISA; autoantibodies; desmoglein 3; disease severity; pathogenicity