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Auto‐antibodies to Receptor Tyrosine Kinases TrkA, TrkB and TrkC in Patients with Chronic Chagas’ Disease
Author(s) -
Lu B.,
Petrola Z.,
Luquetti A. O.,
PereiraPerrin M.
Publication year - 2008
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2008.02102.x
Subject(s) - tropomyosin receptor kinase b , tropomyosin receptor kinase a , tropomyosin receptor kinase c , low affinity nerve growth factor receptor , tyrosine kinase , receptor tyrosine kinase , chagas disease , kinase , antibody , neurotrophin , medicine , receptor , immunology , biology , platelet derived growth factor receptor , microbiology and biotechnology , neurotrophic factors , growth factor
The Chagas’ disease parasite Trypanosoma cruzi promotes survival and differentiation of neurones by binding and activating nerve growth factor (NGF) receptor TrkA. The functional mimic of NGF in T. cruzi is a surface‐bound and shed immunogenic protein [neurotrophic factor/ trans ‐sialidase (TS)], which raised the possibility that immune response to T. cruzi in general and to neurotrophic factor/TS in particular leads to loss of immunological tolerance to host NGF and/or the NGF‐binding partner TrkA. In testing this hypothesis, we found that sera of individuals with chronic Chagas’ disease bear unique IgG2 autoantibodies that bind TrkA and TrkA family members TrkB and TrkC (ATA). Binding of ATA to Trk receptors is specific because the autoantibodies did not cross‐react with five other growth factor receptors, NGF and other neurotrophins, and T. cruzi . Thus, individuals with chronic Chagas’ disease produce unique antibodies that react with pan‐Trk receptors, one of which (TrkA) T. cruzi exploits to inhibit host cell apoptosis and to promote cellular invasion.