title: Identification of potential serodiagnostic and subunit vaccine antigens by antibody profiling of toxoplasmosis cases in Turkey.
abstract: Toxoplasmosis, caused by infection of the protozoan parasite Toxoplasma gondii, is associated with mild disease in healthy individuals, whereas individuals with depressed immunity may develop encephalitis, neurologic disorders, and other organ diseases. Women who develop acute toxoplasmosis during pregnancy are at risk of transmitting the infection to the fetus, which may lead to fetal damage. A diagnosis is usually confirmed by measuring IgG, or IgM where it is important to determine the onset of infection. A negative IgM result essentially excludes acute infection, whereas a positive IgM test is largely uninterpretable because IgM can persist for up to 18 months after infection. To identify antigens for improved diagnosis of acute infection, we probed protein microarrays displaying the polypeptide products of 1357 Toxoplasma exons with well-characterized sera from Turkey. The sera were classified according to conventional assays into (1) seronegative individuals with no history of T. gondii infection; (2) acute infections defined by clinical symptoms, high IgM titers, and low avidity IgG; (3) chronic/convalescent cases with high avidity IgG but persisting IgM; (iv) true chronic infections, defined by high avidity IgG and no IgM. We have identified 38 IgG target antigens and 108 IgM target antigens that can discriminate infected patients from healthy controls, one or more of which could form the basis of a 'tier-1' test to determine current or previous exposure. Of these, three IgG antigens and five IgM antigens have the potential to discriminate chronic/IgM persisting or true chronics from recent acutely infected patients (a 'tier-2' test). Our analysis of the antigens revealed several enriched features relative to the whole proteome, which include transmembrane domains, signal peptides, or predicted localization at the outer membrane. This is the first protein microarray survey of the antibody response to T. gondii, and will help in the development of improved serodiagnostics and vaccines.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Mert
authors.initials: M
authors.lastname: Döşkaya
authors.forename: Silvia
authors.initials: S
authors.lastname: Juarez
authors.forename: Ayşe
authors.initials: A
authors.lastname: Caner
authors.forename: Algis
authors.initials: A
authors.lastname: Jasinskas
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Tan
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hajagos
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bradley
authors.forename: Metin
authors.initials: M
authors.lastname: Korkmaz
authors.forename: Yüksel
authors.initials: Y
authors.lastname: Gürüz
authors.forename: Philip L
authors.initials: PL
authors.lastname: Felgner
authors.forename: D Huw
authors.initials: DH
authors.lastname: Davies
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D001185:Artificial Intelligence; D016022:Case-Control Studies; D003198:Computer Simulation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D018448:Models, Immunological; D040081:Protein Array Analysis; D012372:ROC Curve; D012698:Serologic Tests; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D014421:Turkey; D022223:Vaccines, Subunit
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022223:Vaccines, Subunit