Development of an IgG4-based predictor of endemic pemphigus foliaceus (fogo selvagem).
Fogo selvagem (FS) is mediated by pathogenic, predominantly IgG4, anti-desmoglein 1 (Dsg1) autoantibodies and is endemic in Limao Verde, Brazil. IgG and IgG subclass autoantibodies were tested in a sample of 214 FS patients and 261 healthy controls by Dsg1 ELISA. For model selection, the sample was randomly divided into training (50%), validation (25%), and test (25%) sets. Using the training and validation sets, IgG4 was chosen as the best predictor of FS, with index values above 6.43 classified as FS. Using the test set, IgG4 has sensitivity of 92% (95% confidence interval (95% CI): 82-95%), specificity of 97% (95% CI: 89-100%), and area under the curve of 0.97 (95% CI: 0.94-1.00). The IgG4 positive predictive value (PPV) in Limao Verde (3% FS prevalence) was 49%. The sensitivity, specificity, and PPV of IgG anti-Dsg1 were 87, 91, and 23%, respectively. The IgG4-based classifier was validated by testing 11 FS patients before and after clinical disease and 60 Japanese pemphigus foliaceus patients. It classified 21 of 96 normal individuals from a Limao Verde cohort as having FS serology. On the basis of its PPV, half of the 21 individuals may currently have preclinical FS and could develop clinical disease in the future. Identifying individuals during preclinical FS will enhance our ability to identify the etiological agent(s) triggering FS.
Qaqish
Bahjat F
BF
Department of Biostatisitcs, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Prisayanh
Phillip
P
Qian
Ye
Y
Andraca
Eugenio
E
Li
Ning
N
Aoki
Valeria
V
Hans-Filho
Gunter
G
dos Santos
Vandir
V
Rivitti
Evandro A
EA
Diaz
Luis A
LA
D000293:Adolescent; D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods*; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism; D007564:Japan; D008954:Models, Biological; D010392:Pemphigus / Q000175:diagnosis* / Q000276:immunology*; D011237:Predictive Value of Tests
D007074:Immunoglobulin G