•"Antibody repertoire of patients with chronic Chagas´ Heart Disease".

VANINA GRIPPO, LETICIA NIBORSKI, EVELYN MAHLER, FERNANDO E. ELIAS, CLAUDIA BEREK, MARIANO J. LEVIN.

Río de Janeiro, Brasil

Congreso; 13th Congreso Internacional de Inmunología. Río de Janeiro; 2007

Patients with chronic Chagas´ Heart Disease (cChHD) develop an antibody response that is suspected to be involved in the cardiac pathogenesis. To better understand it we constructed a Fab combinatorial library derived from a cChHD patient´s bone marrow. In addition, we also cloned and characterized antibody (Ab) variable regions from single plasma cells isolated from heart biopsies from three other patients. The phage library was panned against T. cruzi lysate and T. cruzi P2 ribosomal protein using a novel method for elution. We obtained recombinant antibodies that specifically reacted with T. cruzi antigens. Furthermore, we analyzed cChHD patient repertoire and distribution of a total of 148 rearranged VH genes and compared with the repertoire of patients with autoimmune diseases. Amongst the anti-T.cruzi Abs a VH4 overrepresentation was found (mostly VH4-59 and VH4-39). Plasma cells at the site of cardiac infiltration showed a high usage of VH1. CDR3 region compositions were somewhat different between the phage display library and the in vivo repertoire obtained from plasma cells, indicating a higher degree of affinity maturation among the latter, confirmed by somatic mutation analysis. CDR3 lengths were similar to the ones found in the healthy repertoire and significantly shorter than what has been observed among other chronic infections. We also compared the cChHD repertoire with VH obtained from the sites of heart infiltration. No resemblance of the cChHD repertoire with that of autoimmune patients was found.