Mapping the antigenicity of the parasites in Leishmania donovani infection by proteome serology.
BACKGROUND
Leishmaniasis defines a cluster of protozoal diseases with diverse clinical manifestations. The visceral form caused by Leishmania donovani is the most severe. So far, no vaccines exist for visceral leishmaniasis despite indications of naturally developing immunity, and sensitive immunodiagnostics are still at early stages of development.


RESULTS
Establishing a proteome-serological methodology, we mapped the antigenicity of the parasites and the specificities of the immune responses in human leishmaniasis. Using 2-dimensional Western blot analyses with sera and parasites isolated from patients in India, we detected immune responses with widely divergent specificities for up to 330 different leishmanial antigens. 68 antigens were assigned to proteins in silver- and fluorochrome-stained gels. The antigenicity of these proteins did not correlate with the expression levels of the proteins. Although some antigens are shared among different parasite isolates, there are extensive differences and no immunodominant antigens, but indications of antigenic drift in the parasites. Six antigens were identified by mass spectrometry.


CONCLUSIONS
Proteomics-based dissection of the serospecificities of leishmaniasis patients provides a comprehensive inventory of the complexity and interindividual heterogeneity of the host-responses to and variations in the antigenicity of the Leishmania parasites. This information can be instrumental in the development of vaccines and new immune monitoring and diagnostic devices.
Forgber
Michael
M
Department of Dermatology, Venerology and Allergy, Charité-Universitätsmedizin Berlin, Humboldt University, Berlin, Germany.
Basu
Rajatava
R
Roychoudhury
Kaushik
K
Theinert
Stephan
S
Roy
Syamal
S
Sundar
Shyam
S
Walden
Peter
P
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000235:genetics / Q000302:isolation & purification; D015153:Blotting, Western; D002648:Child; D015180:Electrophoresis, Gel, Two-Dimensional; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007194:India; D007893:Leishmania donovani / Q000235:genetics / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D020543:Proteome