Identification of tear lipocalin as a novel autoantigen target in Sjögren's syndrome.
Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and tissue damage mainly confined to the salivary and lacrimal glands, resulting in dryness of mouth and eyes. Since different epithelial cells of exocrine and non-exocrine tissues are primarily affected, an autoimmune reaction against antigens commonly expressed in epithelial cells is believed to play a pathogenic role. To identify novel autoantigen targets associated with the systemic involvement in SS, we screened a random peptide library with pooled IgG immunoglobulins derived from patients with primary SS. Among the identified peptides, one was recognized by the majority of patients' sera, but not by sera of normal donors and of patients with other autoimmune diseases. The peptide showed homology with an Epstein-Barr Virus (EBV) derived protein and with tear lipocalin, a protein highly expressed in tears and saliva, and with alpha-fodrin, a cytoskeleton protein considered an important autoantigen target in SS. Anti-peptide antibodies affinity purified from patients' sera recognize the viral protein, tear lipocalin and alpha-fodrin. Our findings suggest that EBV infection may be linked to the pathogenesis of SS and that tear lipocalin can be considered a novel and yet unidentified autoantigen in SS.
Navone
Riccardo
R
Department of Clinical and Experimental Medicine, University of Verona, Policlinico GB Rossi, Piazzale LA Scuro 10, Italy.
Lunardi
Claudio
C
Gerli
Roberto
R
Tinazzi
Elisa
E
Peterlana
Dimitri
D
Bason
Caterina
C
Corrocher
Roberto
R
Puccetti
Antonio
A
D000956:Antigens, Viral / Q000276:immunology; D001324:Autoantigens / Q000302:isolation & purification / Q000378:metabolism*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D019169:Jurkat Cells; D054835:Lipocalin 1; D008840:Microfilament Proteins / Q000276:immunology; D019151:Peptide Library; D012859:Sjogren's Syndrome / Q000276:immunology*; D013666:Tears / Q000276:immunology*; D013049:Spectrin
D000956:Antigens, Viral; D001324:Autoantigens; D002352:Carrier Proteins; D007074:Immunoglobulin G; D054835:Lipocalin 1; D008840:Microfilament Proteins; D019151:Peptide Library; D013049:Spectrin; C518443:LCN1 protein, human