Anti-desmocollin autoantibodies in nonclassical pemphigus

Area of Science:

• Immunodermatology
• Autoimmunity research
• Molecular diagnostics

Background:

• The role of anti-desmoglein (Dsg) antibodies in pemphigus is established, but the significance of autoantibodies targeting desmocollin (Dsc) remains unclear.
• Development of reliable immunoassays for detecting immunoglobulin (Ig) G autoantibodies against Dscs has been lacking.

Purpose of the Study:

• To develop and validate novel enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-Dsc autoantibodies.
• To investigate the prevalence and potential pathogenicity of anti-Dsc antibodies in various pemphigus subtypes.

Main Methods:

• Expression of soluble recombinant proteins (RPs) of human Dsc1-3 in mammalian cells.
• Utilized novel ELISAs with mammalian Dsc RPs to analyze sera from pemphigus patients, including 79 with paraneoplastic pemphigus (PNP).
• Compared mammalian ELISAs with baculoprotein ELISAs and complementary DNA (cDNA) transfection methods for sensitivity and specificity.

Main Results:

• Mammalian ELISAs detected IgG autoantibodies to Dsc1, Dsc2, and Dsc3 in 16.5%, 36.7%, and 59.5% of PNP sera, respectively.
• Significant reactivity with Dsc1 and Dsc3 was observed in sera from pemphigus herpetiformis (PH) and pemphigus vegetans (PVeg).
• Mammalian ELISAs demonstrated higher specificity and sensitivity compared to alternative methods; some PH sera lacked reactivity to Dsgs, and PNP/PVeg reactivity to Dscs was not abrogated by Dsg RP pre-absorption.

Conclusions:

• Novel ELISAs reveal frequent detection of IgG anti-Dsc autoantibodies in pemphigus.
• These anti-Dsc antibodies are potentially pathogenic, particularly in nonclassical pemphigus variants like PH and PVeg.
• The developed assays provide a reliable tool for diagnosing and understanding the role of anti-Dsc antibodies in pemphigus pathogenesis.