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Master's Dissertation
DOI
https://doi.org/10.11606/D.5.2008.tde-23012009-121037
Document
Author
Full name
Susanne Carolinne Penha Ferreira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Kalil Filho, Jorge Elias (President)
Barros, Myrthes Anna Maragna Toledo
Silva Filho, Álvaro Pacheco e
Title in Portuguese
Detecção de estruturas renais reconhecidas por anticorpos não-HLA envolvidos na rejeição humoral em pacientes transplantados renais
Keywords in Portuguese
Anticorpos
Rejeição de enxerto
Transplante de rim
Abstract in Portuguese
O transplante de órgãos é hoje uma opção de tratamento de várias doenças terminais. Apesar de todos os progressos no campo do transplante, o principal problema enfrentado ainda é a rejeição. As principais moléculas responsáveis pela resposta alogeneica e subsequente rejeição ao enxerto, são os antígenos leucocitários humanos (HLA, do inglês Human Leucocyte Antigens). Porém, existem evidências que anticorpos dirigidos a antígenos não-HLA estão associados com rejeição de transplantes. Neste estudo, foi investigada a presença de anticorpos anti-célula endotelial (AACE) em 11 pacientes que perderam seus rins transplantados devido à rejeição humoral irreversível e em 2 com perda por trombose de veia renal. A ausência de anticorpos anti-HLA contra o doador foi verificada antes do transplante, da rejeição e antes e depois da transplantectomia, através da realização de provas cruzadas usando as técnicas mais sensíveis. Anticorpos não-HLA presentes em nove eluatos reagiram com EAHy.926. Eluatos positivos e negativos contra linhagem EAHy.926 foram testados contra cortes histológicos de 6 rins sadios para detecção de quais estruturas renais são reconhecidas por esses anticorpos. A reação foi avaliada pelo método de imunofluorescência indireta. Dos 13 eluatos testados, 4 (isotipo IgG) e 5 (isotipo IgM) reagiram com forte fluorescência nos glomérulos e endotélio arterial, mas não foi verificada reação na cápsula de Bowman e no epitélio tubular. Não foi observado polimorfismo na reatividade dos eluatos. Em onclusão, verificamos que os anticorpos não-HLA têm um importante papel na rejeição humoral. Estes estão reconhecendo antígenos de um sistema provavelmente não-polimórfico nas células de endoteliais presentes, principalmente, nos capilares glomerulares.
Title in English
Detection of renal structures recognized by non-HLA antibodies involved in the humoral rejection in patients with renal transplants
Keywords in English
Antibodies
Graft rejction
Kidney transplantation
Abstract in English
The transplant of organs is today an option of treatment to several terminal diseases. In spite of all the progress in the field of the transplants, the rejection remains a problem to be solved. The main target molecules for the allogenic response and subsequent allograft rejection are the human leukocyte antigens (HLA). However, there are growing evidences that non-HLA antibodies are associated with transplant rejection. In this study it was investigated the presence of anti-endothelial cell antibodies (AECA) in 11 patients who had early lost their transplanted kidney by irreversible humoral rejection and in 2 ones from renal venal thrombosis. The absence of anti-HLA antibodies against the donor was verified by the negativity of crossmatches performed using the most sensitive assays, at the transplant, at the rejection, and before and after the transplantectomy Antibodies from 9 eluates bound to EAHy.926. Positive and negatives eluates were tested against frozen sections from 6 normal kidneys in order to define the structures to which they were reactive. The reactivity was identified by indirect immunofluorescence method. From 13 eluates evaluated, 4 (isotipe IgG) and 5 (isotipe IgM) reacted to the glomerulus and renal arterial endothelium with intense fluorescence but they did not react to the Bowmans capsule and tubular epithelium. No polymorphism was observed in eluates reactivity. In conclusion, we have shown that non-HLA antibodies may represent a cause of the humoral rejection. These antibodies are probably recognizing antigens of a nonpolymorphic system in endothelial cells present, mainly, in the glomerular capillaries.
 
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Publishing Date
2009-01-28
 
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