The heavy chain variable segment gene repertoire in chronic Chagas' heart disease

The Journal of Immunology : Official Journal of the American Association of Immunologists
Vanina GrippoMariano J Levin

Abstract

Patients chronically infected with Trypanosoma cruzi develop chronic Chagas' heart disease (cChHD). Their Ab response is suspected to be involved in the cardiac pathogenesis. Reactivity of serum Abs from these patients has been extensively studied but little is known about the diversity of the in vivo IgG repertoire. We analyzed 125 variable H chain (VH) genes and compared it to repertoires from healthy individuals, and patients with autoimmune processes and other infections. VH were from plasma cells isolated from heart tissue of three cChHD patients and from a Fab combinatorial library derived from bone marrow of another cChHD patient. The role of the parasite in shaping the Ab repertoire was assessed analyzing VH genes before and after panning against T. cruzi Ag. Among recovered VH genes, a significantly increased representation of VH4 was observed. Plasma cells at the site of cardiac infiltration showed an increased VH1 usage. CDR3 lengths were similar to the ones found in the healthy repertoire and significantly shorter than in other infections. VH derived from anti-T. cruzi Fab and plasma cells showed a higher proportion of hypermutated genes, 46.9% and 43.75%, respectively, vs 30.9% of the cChHD patient repertoire, poin...Continue Reading

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Citations

Mar 19, 2011·Parasitology·Vanina GrippoMariano J Levin
Oct 20, 2010·Drug Design, Development and Therapy·Werner Apt
Nov 23, 2017·International Journal of Molecular Sciences·Anizah RahumatullahTheam Soon Lim
Oct 5, 2019·Scientific Reports·Nancy ChaayaSéverine Padiolleau-Lefèvre

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