Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system.

Niborski, Leticia Laura; Potenza, Mariana; Chirivi, Renato G. S.; Simonetti, Leandro; Ossowski, Micaela Soledad; Grippo, Vanina; May, María; Staquicini, Daniela I.; Parodi-Talice, Adriana; Robello, Carlos; Comini, Marcelo A.; Alonso, Guillermo V.; Raats, Jos; Gómez, Karina Andrea

doi:10.1016/j.ebiom.2020.103206

Cited by 5 publications

(6 citation statements)

References 92 publications

(62 reference statements)

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“…In recent work, we demonstrated that the scFv A2R1 recognizes tubulin expressed in all forms of T. cruzi as well as in other members of the kinetoplastid family, and this antigen-antibody interaction depends on any post-translational modifications contained in the protein. Interestingly, we also showed that scFv A2R1 binds to mammal tubulin present in the peripheral and central nervous system, supporting the notion that an autoreactive phenomenon occurs in chronically infected patients, and this could be linked to the pathophysiology of Chagas disease [24].…”

Section: Introductionsupporting

confidence: 81%

“…As mentioned above, scFv 6B6 was isolated from antibody phage-display libraries constructed from the B cell cDNA of CCD subjects and screened against the T. cruzi parasite lysate coated on an immunotube [24,25]. The antibody was then expressed and purified from E. coli.…”

Section: The Scfv 6b6 Specifically Recognizes a Protein From T Cruzi ...mentioning

confidence: 99%

“…With the intention to deeply investigate the anti-T. cruzi antibody repertoire, our laboratory has performed phage display libraries derived from the B-cell mRNA of patients with CCD and cardiac disorders, constructed using either Fab or single-chain variable fragment (scFv) formats [22,23]. One of the scFv libraries screened against the T. cruzi epimastigote parasite lysate allowed the isolation of different monoclonal antibodies, each one with its own binding capacity and protein specificity [24]. In recent work, we demonstrated that the scFv A2R1 recognizes tubulin expressed in all forms of T. cruzi as well as in other members of the kinetoplastid family, and this antigen-antibody interaction depends on any post-translational modifications contained in the protein.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Novel Trypanosoma cruzi-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease

Ossowski,

Gallardo,

Niborski

et al. 2024

IJMS

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Chagas disease is caused by the parasite Trypanosoma cruzi. In humans, it evolves into a chronic disease, eventually resulting in cardiac, digestive, and/or neurological disorders. In the present study, we characterized a novel T. cruzi antigen named Tc323 (TcCLB.504087.20), recognized by a single-chain monoclonal antibody (scFv 6B6) isolated from the B cells of patients with cardiomyopathy related to chronic Chagas disease. Tc323, a ~323 kDa protein, is an uncharacterized protein showing putative quinoprotein alcohol dehydrogenase-like domains. A computational molecular docking study revealed that the scFv 6B6 binds to an internal domain of Tc323. Immunofluorescence microscopy and Western Blot showed that Tc323 is expressed in the main developmental forms of T. cruzi, localized intracellularly and exhibiting a membrane-associated pattern. According to phylogenetic analysis, Tc323 is highly conserved throughout evolution in all the lineages of T. cruzi so far identified, but it is absent in Leishmania spp. and Trypanosoma brucei. Most interestingly, only plasma samples from patients infected with T. cruzi and those with mixed infection with Leishmania spp. reacted against Tc323. Collectively, our findings demonstrate that Tc323 is a promising candidate for the differential serodiagnosis of chronic Chagas disease in areas where T. cruzi and Leishmania spp. infections coexist.

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Section: Introductionsupporting

confidence: 81%

Section: The Scfv 6b6 Specifically Recognizes a Protein From T Cruzi ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of Novel Trypanosoma cruzi-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease

Ossowski,

Gallardo,

Niborski

et al. 2024

IJMS

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“… 7 , 46 However, the precise inflammatory role of these antibodies in cardiac fibers remains complex, and there is limited information regarding the progression of cardiac damage from mild to severe or the maintenance of cardiac integrity. 47 , 48 Notably, a retrospective longitudinal cohort study 15 demonstrated a correlation between elevated IgG1 levels and left ventricular ejection fraction dysfunction. The authors suggested a potential association with cardiomyopathies, as the kinetics of anti- T. cruzi antibodies indicate a progression toward SC damage, which could have prognostic implications for cardiac diseases.…”

Section: Discussionmentioning

confidence: 99%

IgG Isotypes Targeting a Recombinant Chimeric Protein of Trypanosoma cruzi in Different Clinical Presentations of Chronic Chagas Disease

Serrano,

Ribeiro,

Santos

et al. 2024

The American Journal of Tropical Medicine and Hygiene

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Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, which leads to a spectrum of clinical presentations that range from asymptomatic to severe cardiac involvement. The host immune response plays a pivotal role in disease progression. Ig isotypes may contribute to disease pathogenesis. Investigating these components can provide insights into the immunopathogenic mechanisms underlying CD. This cross-sectional study aims to establish a correlation between the Ig profile of individuals infected with T. cruzi with the clinical forms of chronic CD. Serum samples were collected from partner institutions in different states of Brazil. Individuals diagnosed with chronic CD were categorized based on the clinical form of the disease. The indirect ELISA method using the recombinant chimeric Molecular Biology Institute of Paraná membrane protein 8.4 as the antigen was used to determine the Ig profile, including total IgG, IgG1, IgG2, IgG3, and IgG4. Ninety-seven serum samples from patients classified as negative (NEG, n = 38), indeterminate (IND, n = 24), mild cardiac (MC, n = 20), and severe cardiac (SC, n = 15) forms were analyzed. IgG1 exhibited greater levels compared with the other isotypes, showing a significant difference between the MC and IND groups. IgG3 levels were greater in individuals from the MC group compared with the SC group. IgG1 and IgG3 isotypes can serve as biomarkers to evaluate the progression of CD because they exhibit variations across clinical groups. Additional longitudinal studies are necessary to explore the relationship between antibody kinetics and the development of tissue damage.

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“…In addition, an important new motif of trans- sialidase/gp85 (TS9) and the receptor on the host cell that binds to gp85, the prokineticin-2 receptor (PKR2), has been identified ( Tonelli et al, 2010 ; Khusal et al, 2015 ; Teixeira et al, 2015 ). Recently, phage display has been used to study immune response in order to find new epitopes and antigens or to understanding pathological manifestation in Chagas Disease ( Niborski et al, 2021 ; Teixeira et al, 2021 ). Furthermore, phage display screening led to the identification of a peptide (named EPI18) that binds to the surface of the non-infective epimastigote form ( Sáenz-Garcia et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

The Screen of a Phage Display Library Identifies a Peptide That Binds to the Surface of Trypanosoma cruzi Trypomastigotes and Impairs Their Infection of Mammalian Cells

Paula¹,

Lopes-Torres

Jacobs-Lorena

et al. 2022

Front. Microbiol.

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BackgroundChagas is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. On the order of seven million people are infected worldwide and current therapies are limited, highlighting the urgent need for new interventions. T. cruzi trypomastigotes can infect a variety of mammalian cells, recognition and adhesion to the host cell being critical for parasite entry. This study focuses on trypomastigote surface ligands involved in cell invasion.MethodsThree selection rounds of a phage peptide display library for isolation of phages that bind to trypomastigotes, resulted in the identification of the N3 dodecapeptide. N3 peptide binding to T. cruzi developmental forms (trypomastigotes, amastigotes and epimastigotes) was evaluated by flow cytometry and immunofluorescence assays. Parasite invasion of Vero cells was assessed by flow cytometry and immunofluorescence assays.ResultsPhage display screening identified the N3 peptide that binds preferentially to the surface of the trypomastigote and amastigote infective forms as opposed to non-infective epimastigotes. Importantly, the N3 peptide, but not a control scrambled peptide, inhibits trypomastigote invasion of Vero cells by 50%.ConclusionThe N3 peptide specifically binds to T. cruzi, and by doing so, inhibits Vero cell infection. Follow-up studies will identify the molecule on the parasite surface to which the N3 peptide binds. This putative T. cruzi ligand may advance chemotherapy design and vaccine development.

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Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system.

Cited by 5 publications

References 92 publications

Characterization of Novel Trypanosoma cruzi-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease

Characterization of Novel Trypanosoma cruzi-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease

IgG Isotypes Targeting a Recombinant Chimeric Protein of Trypanosoma cruzi in Different Clinical Presentations of Chronic Chagas Disease

The Screen of a Phage Display Library Identifies a Peptide That Binds to the Surface of Trypanosoma cruzi Trypomastigotes and Impairs Their Infection of Mammalian Cells

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