Biomaterial Database

Human antibody responses to Trypanosoma cruzi 70-kD heat-shock proteins. 1998

G M Krautz, and J D Peterson, and L M Godsel, and A U Krettli, and D M Engman

Departamento de Bioquimica e Immunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais e Centro de Pesquisas Rene Rachou Fiocruz, Belo Horizonte, Brazil.

Heat-shock proteins of the 70-kD (hsp70) family are targets of humoral and cellular immune responses following bacterial or parasitic infections, including Chagas' disease. In the present study, we measured antibodies in human sera reactive with hsp70s from the cytoplasm (cy-hsp70), mitochondrion (mt-hsp70), and endoplasmic reticulum (grp78) of Trypanosoma cruzi. Of the three hsp70s tested, only grp78 detected T. cruzi infection in more than 90% of nontreated (NT) patients, with cy-hsp70 and mt-hsp70 detecting only 78% and 25% of NT patients, respectively. Reactivity of leishmanial sera was 77% with cy-hsp70, 13% with grp78, and 5% with mt-hsp70. Therefore, considering sensitivity and specificity, the best candidate for T. cruzi serodiagnosis is grp78. Combination of grp78 with a T. cruzi 24-kD flagellar calcium binding protein (FCaBP) increased the diagnostic sensitivity from 90% to 97% but increased leishmanial reactivity from 3% to 8%. To determine whether hsp70s are useful for discriminating between cured and noncured patients treated with trypanocidal drugs, we tested sera from treated noncured (TNC) patients and cured patients who have positive conventional serology, termed treated dissociated (TD). The cy-hsp70 and grp78 reacted with 74% and 68% of TNC patient sera, respectively, but these antigens did not discriminate TNC from TD patients (52% and 45% positive, respectively). The mt-hsp70 was detected by sera from few TNC patients (18%) and no TD patients. Although individual hsp70s were not useful for determining the effect of trypanocidal drugs on T. cruzi infection in individual patients, the majority of TNC patient sera (70-80%) reacted with two or three of the hsp70s. In contrast, no TD sera reacted with all three hsp70s, and 40% did not react with any of the hsp70s, indicating that the number of hsp70s detected decreases following successful treatment. Considered together, these results show that grp78 has potential as a diagnostic antigen and that absence of reactivity to all three hsp70s may be indicative of effective treatment.

UI	MeSH Term	Description	Entries
D007891	Leishmania	A genus of flagellate protozoa comprising several species that are pathogenic for humans. Organisms of this genus have an amastigote and a promastigote stage in their life cycles. As a result of enzymatic studies this single genus has been divided into two subgenera: Leishmania leishmania and Leishmania viannia. Species within the Leishmania leishmania subgenus include: L. aethiopica, L. arabica, L. donovani, L. enrietti, L. gerbilli, L. hertigi, L. infantum, L. major, L. mexicana, and L. tropica. The following species are those that compose the Leishmania viannia subgenus: L. braziliensis, L. guyanensis, L. lainsoni, L. naiffi, and L. shawi.	Leishmania (Leishmania),Leishmania (Viannia),Leishmania leishmania,Leishmania viannia,Leishmania leishmanias,Leishmania viannias,Leishmanias,Leishmanias (Leishmania),Leishmanias (Viannia),leishmanias, Leishmania,viannias, Leishmania
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D003429	Cross Reactions	Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.	Cross Reaction,Reaction, Cross,Reactions, Cross
D003593	Cytoplasm	The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)	Protoplasm,Cytoplasms,Protoplasms
D004721	Endoplasmic Reticulum	A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)	Ergastoplasm,Reticulum, Endoplasmic
D004797	Enzyme-Linked Immunosorbent Assay	An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.	ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000091342	Endoplasmic Reticulum Chaperone BiP	An ENDOPLASMIC RETICULUM specific chaperone of the HSP70 family. They are involved in folding and oligomerization of secreted and membrane proteins and ENDOPLASMIC RETICULUM STRESS related UNFOLDED PROTEIN RESPONSE.	Binding-immunoglobulin Protein Molecular Chaperone,Glucose Regulated Protein 78 kDa,Grp78,HSPA5 Protein,Heat-Shock Protein 5,Molecular Chaperone BiP,Molecular Chaperone GRP78,BiP, Molecular Chaperone,Binding immunoglobulin Protein Molecular Chaperone,GRP78, Molecular Chaperone,Heat Shock Protein 5,Protein, HSPA5
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia