Study about Natural Killer cells (NK cells) in antibody-mediated rejection: role of NK cells in the C4d-Negative humoral rejection

• Grant number: 12/21604-9
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2013
• End date: August 31, 2015
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Denise Maria Avancini Costa Malheiros
• Grantee: Denise Maria Avancini Costa Malheiros
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Daniela Cristina dos Santos Souza ; Niels Olsen Saraiva Câmara

Abstract

The antibody-mediated rejection with unquestinable importance in the prognosis of the allograft, is characterized by the presence of low levels of detectable preformed antibodies or by formed antibodies post-transplant, C4d deposition in peritubular capillaries and morphological evidence suggestive of humoral rejection. However, the absence of C4d deposition does not exclude the possibility of humoral rejection caused by another mechanism non complement fixation. Cells of the innate immune response, as the Natural Killer cells (NKcells) and macrophages, can make part of this other mechanism. NK cells can affect target endothelial cells through antibody dependent cellular cytotoxicity (ADCC). ADCC is triggered by interaction of FcyRIII on NK cells with immunoglobulin bound to antigen on target cells, leading to NK activation. Recent findings, by immunostaining, have demonstrated that CD56+ and CD68+ cells in peritubular capillaries are increased in antibody-mediated rejection as well as evidences of endothelial injury caused by interaction between NK cells and Fc immunoglobulin portion. In order to search for new diagnostic markers of early humoral rejection, this study aims to compare the immunoreactivity of NK cells and macrophages in acute and chronic antibody-mediated rejection with presence or absence for C4d deposition, to evaluate the expression of cells in cases where there were observed morphological evidence suggesting humoral rejection and to establish relationship between this results and the graft survival. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DOS SANTOS, DANIELA CRISTINA; CAMPOS, ERIKA FERNANDES; SARAIVA CAMARA, NIELS OLSEN; RIBEIRO DAVID, DAISA SILVA; AVANCINI COSTA MALHEIROS, DENISE MARIA. Compartment-specific expression of natural killer cell markers in renal transplantation: immune profile in acute rejection. Transplant International, v. 29, n. 4, p. 443-452, APR 2016. (12/21604-9)

DOS SANTOS, DANIELA CRISTINA; SARAIVA CAMARA, NIELS OLSEN; RIBEIRO DAVID, DAISA SILVA; AVANCINI COSTA MALHEIROS, DENISE MARIA. Expression patterns of CD56+and CD16+cells in renal transplant biopsies with acute rejection: Associations with microcirculation injuries and graft survival. NEPHROLOGY, v. 22, n. 12, p. 993-1001, DEC 2017. (12/21604-9)