Retinal dysfunction in patients with chronic Chagas' disease is associated to anti‐Trypanosoma cruziantibodies that cross‐react with rhodopsin

Abstract

To investigate retinal involvement in chronic Chagas' disease, we performed electroretinography and retinal fluorescein angiography studies in chagasic patients. Our results demonstrated a dissociated electrophysiological response characterized by both an abnormal reduction of the electroretinographic b-wave amplitude and a delayed latency, under the dark-adaptated condition. These alterations are compatible with a selective dysfunction of the rods. Antibodies raised against Trypanosoma cruzi that also interact with beta1-adrenergic receptor blocked light stimulation of cGMP-phosphodiesterase in bovine rod membranes. The specificity from the antibody-rhodopsin interaction was confirmed by Western blot analysis and antigenic competition experiments. Our results suggest an immunomediated rhodopsin blockade. T. cruzi infection probably induces an autoimmune response against rhodopsin in the chronic phase of Chagas' disease through a molecular mimicry mechanism similar to that described previously on cardiac human beta1-adrenergic and M2-cholinergic receptors, all related to the same subfamily of G-protein-coupled receptors.

Three-dimensional studies of pathogenic peptides from the c-terminal of Trypanosoma cruziribosomal P proteins and their interaction with a monoclonal antibody structural model

“…This fact strongly reinforces the results of studies that have associated the dysfunction of the retina in chagasic patients with an autoimmune mechanism in which anti-P auto-antibodies would cross-react with the visual pigment rhodopsin [13]. Our findings also support one of the conclusions of a previous study by Soares et al .…”

Structural basis of the cross‐reaction between an antibody to theTrypanosoma cruziribosomal P2β protein and the human β1adrenergic receptor

“…Notably, the model predicts that 20 of the residues that contact the parasite peptide would also contact the peptide of the ␤ 1 -AR, explaining the cross-reactive nature of the mAb 17.2 and its derived recombinants. This model may also explain the cross-reaction of mAb 17.2 with rhodopsin (22).…”

Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection

“…In the retina, TP are expressed on multiple cell types including photoreceptors and ECs (51). The production of TXA 2 by parasites in the orbit may therefore directly contribute to the retinal dysfunction and decreased vascularization observed in chronic Chagas' disease (52). Thus, the persistence of TXA 2 -producing parasites in multiple tissues may directly contribute to the development of the clinical symptoms observed in chronic Chagas' disease.…”