Autoantibodies to neurotrophic receptors TrkA, TrkB and TrkC in patients with acute Chagas' disease.
Neurotrophic receptors TrkA and TrkC double up as receptors that Trypanosoma cruzi uses to invade cells and as autoantigen in T. cruzi-infected individuals (with Chagas' disease). Consequently, autoantibodies against TrkA and TrkC (ATA) potently block T. cruzi invasion in vitro and in ATA-immunized mice. Thus, ATA could keep T. cruzi invasion in check in Chagas' disease. However, ATA has been examined only in patients with chronic Chagas' disease. To determine whether ATA potentially participate in the early stage of infection, we analysed the sera of 15 patients with acute Chagas' disease, 4-66 years of age. We find that all sera contain high antibody titres to TrkA, TrkB and TrkC, but not to other growth factor receptors, indicating that ATA are produced relatively soon after T. cruzi infection by an age-independent process. One individual, who acquired the disease after an accidental laboratory infection, converted to Trk-antibody (Ab)-seronegative when progressing to the chronic phase. ATA from acute patients were of low avidity (K(0) <24.8 x 10(-8) m) and of IgM and IgA isotypes. In contrast, ATA from chronic patients were of high avidity (K(o) = 1.4 to 4.5 x 10(-8) m) and of the IgG2 isotype. Therefore, ATA underwent affinity maturation and class switch when patients progressed from acute to chronic disease. Thus, it may be that Trk autoimmunity, which starts in the acute Chagas' disease, plays a role in attenuating parasitemia and tissue parasitism that characterizes the acute/chronic phase transition of Chagas' disease.
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Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Luquetti
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Rassi
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PereiraPerrin
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001938:Brazil; D014355:Chagas Disease / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D051379:Mice; D008875:Middle Aged; D020917:Receptor, trkA / Q000276:immunology*; D020813:Receptor, trkB / Q000276:immunology*; D020812:Receptor, trkC / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D055815:Young Adult
D000913:Antibodies, Protozoan; D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC