Anti-Trypanosoma cruzi Cross-Reactive Antibodies Detected at High Rate in Non-Exposed Individuals Living in Non-Endemic Regions: Seroprevalence and Association to Other Viral Serologies

Abstract

Cross-reactive antibodies are characterized by their recognition of antigens that are different from the trigger immunogen. This happens when the similarity between two different antigenic determinants becomes adequate enough to enable a specific binding with such cross-reactive antibodies. In the present manuscript, we report the presence, at an “abnormal” high frequency, of antibodies in blood samples from French human subjects cross-reacting with a synthetic-peptide antigen derived from a Trypanosoma cruzi (T. cruzi) protein sequence. As the vector of T. cruzi is virtually confined to South America, the parasite is unlikely to be the trigger immunogen of the cross-reactive antibodies detected in France. At present, the cross-reactive antibodies are measured by using an in-house ELISA method that employs the T. cruzi -peptide antigen. However, to underline their cross-reactive characteristics, we called these antibodies “Trypanosoma cruzi Cross Reactive Antibodies” or TcCRA. To validate their cross-reactive nature, these antibodies were affinity-purified from plasma of healthy blood donor and were then shown to specifically react with the T. cruzi parasite by immunofluorescence. Seroprevalence of TcCRA was estimated at 45% in serum samples of French blood donors while the same peptide-antigen reacts with about 96% of T. cruzi -infected Brazilian individuals. In addition, we compared the serology of TcCRA to other serologies such as HSV 1/2, EBV, HHV-6, CMV, VZV, adenovirus, parvovirus B19, mumps virus, rubella virus, respiratory syncytial virus, measles and enterovirus. No association was identified to any of the tested viruses. Furthermore, we tested sera from different age groups for TcCRA and found a progressive acquisition starting from early childhood. Our findings show a large seroprevalence of cross-reactive antibodies to a well-defined T. cruzi antigen and suggest they are induced by a widely spread immunogen, acquired from childhood. The etiology of TcCRA and their clinical relevance still need to be investigated.

The CXCL10/CXCR3 Axis and Cardiac Inflammation: Implications for Immunotherapy to Treat Infectious and Noninfectious Diseases of the Heart

“…Chagas heart disease is characterized by marked inflammation and fibrosis of the heart, along with cardiac edema, myofibrillar destruction, chamber dilation, and loss of contractile function. The etiology of Chagas heart disease is not fully understood and likely multifactorial, with a contribution of an autoimmune response due in part to molecular mimicry between antigenic determinants of T. cruzi and human (cardiac) antigens [ 62 , 63 ]. With heart failure in Chagas disease, myocardial levels of CD8 + and CD4 + T cells are increased, with a predominance of CD8 + T cells [ 61 , 64 , 65 ].…”

Trypanosoma-Cruzi Cross-Reactive Antibodies Longitudinal Follow-Up: A Prospective Observational Study in Hematopoietic Stem Cell Transplantation

“…TcCRA are newly discovered antibodies of unknown origin, which might be the result of infection with an asymptomatic latent agent [ 1 ]. In the present study, we prospectively evaluated the expression and dynamics of TcCRA in 47 pairs of adult HSCT donors/recipients.…”

“…TcCRA were measured in serum samples using an in-house ELISA test. The used method and reagents are described in SABA et al 2013 [ 1 ]. All the collected samples were tested in duplicate at least one time, if necessary twice, for validation.…”

“…These specific antibodies were named “ Trypanosoma cruzi Cross Reactive Antibodies” (TcCRA) to stress out the fact that they were induced by another antigen than the one from T . cruzi , the causative agent of Chagas disease [ 1 ]. Focusing on opportunistic infection, we investigated TcCRA in patients undergoing allogeneic hematopoietic stem cells transplantation (allo-HSCT) and explored its potential impact on transplantation outcomes.…”

Identification of human linear B-cell epitope sites on the envelope glycoproteins of Crimean-Congo haemorrhagic fever virus

“…However peptides mimicking epitopic or immunodominant regions from conserved regions of the glycoprotein may be useful for serological assay development particularly for serosurveillance which is important for monitoring disease endemicity. Peptide-based ELISA assays have previously been used for the diagnosis and serosurveillance of diverse organisms including hepatitis A virus, monkeypox virus and Trypanosoma cruzi [16–18]. We identified two potential linear B-cell epitope sites on the G C protein.…”