Immunization with recombinant Trypanosoma cruzi ribosomal P2β protein induces changes in the electrocardiogram of immunized mice

• Published in: FEMS immunology and medical microbiology Vol. 18; no. 1; pp. 75 - 85
• Main Authors: Bergami, Pablo Lopez, Meckert, Patricia Cabeza, Kaplan, Dan, Levitus, Gabriela, Elias, Fernando, Quintana, Francisco, Van Regenmortel, Marc, Laguens, Rubén, Levin, Mariano Jorge
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.1997; Oxford University Press
• Subjects: Amino acid sequence; Amino acids; Animal models; Antibodies; Biological activity; BSA, bovine serum albumin; Cardiac muscle; Cardiovascular disease; Cardiovascular diseases; cChHD, chronic Chagas heart disease; Chagas disease; Cloning; Conserved sequence; Coronary artery disease; EKG; EKG, electrocardiogram; Electrocardiogram; Electrocardiography; ELISA, enzyme‐linked immunosorbent assay; Enzyme-linked immunosorbent assay; Epitopes; Functional assay; Functional testing; Heart; Heart diseases; IFA, incomplete Freund adjuvant; IgG, immunoglobulin G; Immune response (humoral); Immunization; Inflammation; MBP, maltose binding protein; Muscles; PBS, phosphate‐buffered saline; PCR, polymerase chain reaction; Polypeptides; Proteins; Protozoa; Ribosomal P protein; Signs and symptoms; SLE, systemic lupus erythematosus; TcP2β, Trypanosoma cruzi ribosomal P2β protein; Trypanosoma cruzi; Vector-borne diseases; βgal, β‐galactosidase; Heart; Chagas disease; Ribosomal P protein; Immunization; Functional assay; Electrocardiogram
• ISSN: 0928-8244; 1574-695X; 2049-632X
• DOI: 10.1111/j.1574-695X.1997.tb01030.x

Abstract Molecular expression cloning techniques revealed that patients with severe chronic Chagas heart disease showed a strong humoral response against the cloned C-terminal portion of the Trypanosoma cruzi ribosomal P2β protein, previously named JL5. The main linear epitope of this polypeptide was mapped to the 13 C-terminal amino acid sequence EEEDDDMGFGLFD (named R13), which is almost identical to the mammalian ribosomal P consensus sequence EESDDDMGFGLFD (named H13). Enzyme-linked immunosorbent assay measurements demonstrated that sera from patients with chronic Chagas heart disease presented a very specific anti-P humoral response with high anti-R13, but low H13 antibody levels. We attempted to develop an animal model that would reproduce, at least partially, two features of the human infection: (1) the serological pattern of the anti-P response, and (2) specific cardiac symptoms. To this effect, mice were immunized with T. cruzi P2β recombinant protein. Immunization reproduced the typical anti-P antibody profile defined for chronic infections, but did not induce cardiac inflammatory lesions. However, it altered significantly the electrocardiograms of immunized mice. It is suggested that this assay represents a functional test for assessing the biological activity of antibodies against T. cruzi ribosomal P protein on cardiac muscle.