A Lutzomyia longipalpis Salivary Protein Induces Cross-Reactive Antibodies to Pemphigus Autoantigen Desmoglein 1.

Autor:	Diaz LA; Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Electronic address: ldiaz@med.unc.edu., Prisayanh P; Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Qaqish B; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Temple BR; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; R.L. Juliano Structural Bioinformatics Core, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Aoki V; Departmento de Dermatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Hans-Filho G; Departmento de Dermatologia, Facultade de Medicina, Universidade Federal of Mato Grosso do Sul, Mato Grosso do Sul, Brazil., Rivitti EA; Departmento de Dermatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Friedman H; Departmento de Patologia, Faculdade de Medicina, Universidade de Brasilia, Brasilia, Brazil., Karetnick M; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA., Herbert SM; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA., Valenzuela JG; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2020 Dec; Vol. 140 (12), pp. 2332-2342.e10. Date of Electronic Publication: 2020 Apr 29.
DOI:	10.1016/j.jid.2020.02.041
Abstrakt:	Fogo selvagem (FS) is a blistering skin disease caused by pathogenic IgG4 autoantibodies to desmoglein 1 (DSG1). Preclinical FS and leishmaniasis are endemic to certain regions of Brazil and exhibit nonpathogenic anti-DSG1 antibodies. Recurring bites from Lutzomyia longipalpis, the sand fly vector of leishmaniasis, immunize individuals with L. longipalpis salivary antigens LJM17 and LJM11. We measured the antibody responses to LJM17, LJM11, and DSG1 in normal settlers and patients with FS from an endemic focus of FS and nonendemic control populations. We also immunized mice with these antigens and assessed the IgG response. Healthy individuals and patients with FS from endemic areas had significantly higher values of IgG4 anti-LJM17 antibodies than nonendemic controls (P < 0.001 for both). The levels of IgG anti-DSG1 and IgG4 anti-LJM17 and anti-LJM11 antibodies correlated positively in normal settlers and patients with FS. Mice immunized with recombinant LJM17 produced IgG1 antibodies (human IgG4 homolog) that strongly cross-reacted with recombinant DSG1; these IgG1 antibodies were inhibited by LJM17, LJM11, and DSG1 in a dose-dependent manner. However, they did not bind human or mouse epidermis by indirect immunofluorescence. Lastly, we identified short-sequence homologies of surface-exposed residues within the human DSG1 ectodomain and LJM17. Inoculation by LJM17 from L. longipalpis-elicited DSG1-cross-reactive IgG4 antibodies may lead to FS in genetically predisposed individuals. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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