The Thomsen-Friedenreich antigen-binding lectin jacalin interacts with desmoglein-1 and abrogates the pathogenicity of pemphigus foliaceus autoantibodies in vivo.

Abstract

Pemphigus foliaceus (PF) is an autoimmune skin blistering disease mediated by pathogenic autoantibodies against the desmosomal core glycoprotein desmoglein-1 (Dsg1). This study demonstrated that the O-glycan-specific plant lectin jacalin binds Dsg1 and inhibits the interaction of Dsg1/PF IgG. N-glycosylation is not involved in the interaction of Dsg1/jacalin or Dsg1/PF IgG. Subcutaneous injection of jacalin into neonatal mice drastically reduced PF IgG deposition at the epidermal cell surface and blocked PF IgG-induced skin blisters, both clinically and histologically. Interestingly, another plant lectin, peanut agglutinin, which shares the same carbohydrate specificity toward the O-linked carbohydrate structure known as Thomsen-Friedenreich antigen (TF antigen, Galβ1-3GalNAcα-O-Ser/Thr), also bound Dsg1 and blocked the skin blistering. In contrast, the plant lectin vicia villosa-B4 (VVL-B4), which shares the carbohydrate specificity toward the O-linked monosaccharide known as Thomsen-nouveau antigen (GalNAc-α1-O-Ser/Thr), did not bind Dsg1 and did not show a protective effect against the disease induced by the autoantibodies. Collectively, these results suggest that the binding of jacalin to O-linked TF carbohydrate motifs on Dsg1 impairs the Dsg1/PF autoantibody interactions and abrogates its pathogenicity in vivo. TF-specific binding ligands may have a potential therapeutic value for PF.

• Authors: Ning Li, Moonhee Park, Minglang Zhao, Julio Hilario-Vargas, David M McInnes, Phillip S Prisayanh, Zhi Liu, Luis A Diaz
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 130 Issue 12 Pg. 2773-80 (Dec 2010) ISSN: 1523-1747 [Electronic] United States
• PMID: 20631728 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adjuvants, Immunologic
• Antigens, Tumor-Associated, Carbohydrate
• Autoantibodies
• DSG1 protein, human
• Desmoglein 1
• Plant Lectins
• jacalin
• Thomsen-Friedenreich antigen

Topics

• Adjuvants, Immunologic (metabolism, pharmacology)
• Animals
• Antigen-Antibody Reactions (drug effects, immunology)
• Antigens, Tumor-Associated, Carbohydrate (immunology, metabolism)
• Autoantibodies (drug effects, immunology, metabolism)
• Desmoglein 1 (immunology, metabolism)
• Epidermis (drug effects, immunology, pathology)
• Glycosylation (drug effects)
• Humans
• Mice
• Mice, Inbred BALB C
• Pemphigus (drug therapy, immunology, pathology)
• Plant Lectins (immunology, metabolism, pharmacology)