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

Antibodies named TcCRA "Trypanosoma cruzi Cross Reactive Antibodies" were detected in 47% of blood donors from French population unexposed to the parasite. In order to evaluate the passive or active transmissibility of TcCRA and further characterize its role and etiology, we have conducted a study in a cohort of 47 patients who underwent allogeneic Hematopoietic Stem Cell Transplantations (allo-HSCT). Donors and recipients were tested for TcCRA prior to transplantation. Recipients were further tested during follow-up after transplantation. Demographical, clinical and biological data were collected. Our primary end-point was to assess the risk of TcCRA acquisition after transplantation. During this initial analysis, we observed no seroconversion in patients receiving cells from TcCRA negative donors (n = 23) but detected seroconversion in 4 out of 24 patients who received hematopoietic stem cells from positive donors. Here, we are discussing possible scenarios to explain TcCRA-immune status in recipient after transplantation.status: publishe

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.

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

Effect of donor’s TcCRA serological status on patients’ TcCRA-signal evolution.

<p>ΔTcCRA was calculated at 3, 6, 9 and 12 months after graft to evaluate the gain or loss in TcCRA signal. The numbers of available samples at 3, 6, 9 and 12 months were respectively 41, 39, 31 and 27.</p

Serology profiles of three different patients including TcCRA, IgG anti-measles virus and IgG anti-mumps virus.

<p>Donor’s serological status is presented for each patient as well. 0.2 (O.D.) represents the cutoff for anti-measles and anti-mumps antibodies.</p

Classification of patients who survived more than 9 months after the transplantation at baseline (BL) and at Follow up (FU) according to their donor’s TcCRA serological status.

<p>Classification of patients who survived more than 9 months after the transplantation at baseline (BL) and at Follow up (FU) according to their donor’s TcCRA serological status.</p

TcCRA profile of four patients during the follow-up.

<p>The X axis represents time in days, where day zero designates the day of engraftment. The Y axis represents TcCRA signals (O.D.) in recipients. Black arrows symbolize the dates of <i>i</i>.<i>v</i>.Ig injections while dotted black lines indicate transfusion periods of other blood-products.</p

SARS-CoV-2 involvement in central nervous system tissue damage

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, it became evident that the SARS-CoV-2 virus infects multiple organs including the brain. Several clinical studies revealed that patients with COVID-19 infection experience an array of neurological signs ranging in severity from headaches to life-threatening strokes. Although the exact mechanism by which the SARS-CoV-2 virus directly impacts the brain is not fully understood, several theories have been suggested including direct and indirect pathways induced by the virus. One possible theory is the invasion of SARS-CoV-2 to the brain occurs either through the bloodstream or via the nerve endings which is considered to be the direct route. Such findings are based on studies reporting the presence of viral material in the cerebrospinal fluid and brain cells. Nevertheless, the indirect mechanisms, including blood-clotting abnormalities and prolonged activation of the immune system, can result in further tissue and organ damages seen during the course of the disease. This overview attempts to give a thorough insight into SARS-CoV-2 coronavirus neurological infection and highlights the possible mechanisms leading to the neurological manifestations observed in infected patients

Demographic variables of the tested samples.

<p>Demographic variables of the tested samples.</p

Immunoreactivity of affinity-purified TcCRA (B) as compared to a negative control that uses irrelevant human antibody (A) on <i>Trypanosoma cruzi</i> epimastigotes as shown by fluorescence microscopy.

<p>The horizontal bar embedded in the image B represents a 20 µm scale.</p

Cumulative seroprevalence of TcCRA in function of age (1 year intervals).

<p>Cumulative seroprevalence of TcCRA in function of age (1 year intervals).</p