Funding sources This study was supported by the Department of Dermatology at the University of Milan (L.L.), the National Institute of Arthritis and Musculoskeletal and Skin Diseases AR053505 and AR057001 (A.S.P.), Deutsche Forschungsgemeinschaft Research Foundation (C.T.E.), T32-AR007465 (A.R.N.), and the Penn Skin Disease Research Center (P30-AR057217).
CLINICAL AND LABORATORY INVESTIGATIONS
Enrichment of total serum IgG4 in patients with pemphigus
Article first published online: 27 SEP 2012
© 2012 The Authors. BJD © 2012 British Association of Dermatologists 2012
British Journal of Dermatology
Volume 167, Issue 6, pages 1245–1253, December 2012
How to Cite
Funakoshi, T., Lunardon, L., Ellebrecht, C.T., Nagler, A.R., O’Leary, C.E. and Payne, A.S. (2012), Enrichment of total serum IgG4 in patients with pemphigus. British Journal of Dermatology, 167: 1245–1253. doi: 10.1111/j.1365-2133.2012.11144.x
Conflicts of interest None declared.
T.F. and L.L. contributed equally to this work.
- Issue published online: 26 NOV 2012
- Article first published online: 27 SEP 2012
- Accepted manuscript online: 14 JUL 2012 10:18AM EST
- Accepted for publication 1 July 2012
Background Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially fatal blistering diseases caused by autoantibodies targeting desmoglein (Dsg) adhesion proteins. Previous studies have shown an IgG4 > IgG1 predominance of anti-Dsg antibodies in pemphigus; however, no studies have examined total serum IgG4 levels in pemphigus. IgG4 is induced by chronic antigen stimulation, which could occur with persistent skin blistering and potentially elevate the total serum IgG4 relative to other IgG subclasses in patients with pemphigus.
Objectives The primary aim of the study was to quantitate total and Dsg-specific IgG subclasses in patients with pemphigus.
Methods IgG subclasses and Dsg-specific IgG1 and IgG4 were quantitated in patients with PV and PF, and in sera from age-matched controls using a subclass enzyme-linked immunosorbent assay. The effectiveness of IgG4 depletion in blocking IgG pathogenicity in PV was determined using a keratinocyte dissociation assay.
Results Dsg-specific antibodies comprised a median of 7·1% and 4·2% of total IgG4 in patients with PV and PF, respectively, with eightfold and fourfold enrichment in IgG4 vs. IgG1. Total serum IgG4, but not other IgG subclasses, was enriched in patients with PV and PF compared with age-matched controls (P = 0·004 and P = 0·005, respectively). IgG4 depletion of PV sera reduced pathogenicity in a keratinocyte dissociation assay and showed that affinity-purified IgG4 is more pathogenic than other serum IgG fractions.
Conclusions Dsg-specific autoantibodies are significantly enriched in IgG4, which may explain the enrichment of total serum IgG4 in some patients with pemphigus. By preferentially targeting autoimmune rather than beneficial immune antibodies, IgG4-targeted therapies may offer safer treatment options for pemphigus.