Significance of immune cell function monitoring in renal transplantation after Thymoglobulin induction therapy.
Monitoring of immune status in transplant recipients is essential for predicting the risk of rejection or infection. In this study, we assessed the significance of immune cell function in 76 renal allograft recipients after Thymoglobulin induction and initiation of maintenance immunosuppression. Using the Immuknow (Cylex Inc) assay, the amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin (PHA) was measured in patients whole blood. In parallel, the frequency and phenotype of CD4+ T cells were determined by flow cytometry. The Immuknow assay yielded paradoxically high ATP values during the first 3 months post-transplantation, despite very low CD4+ T cell counts. High ATP values were caused by peripheral blood myeloid cells, did not predict rejection, and occurred primarily in transplant recipients who received darbepoietin (p = 0.017). CD4+ T cells displayed predominantly an activated/memory phenotype and comprised a subpopulation of CD25+FOXP3+ cells. Over the first 5 months post-transplantation, mean ATP activity gradually decreased, whereas CD4+ T cell counts slowly increased. Low ATP values were predictive of infection (p = 0.002). Thus Immuknow results need to be interpreted with caution in patients receiving Thymoglobulin induction therapy. Although low ATP levels identify patients at increased risk for infection, high ATP values fail to correlate with rejection and do not justify increased immunosuppression.
Serban
Geo
G
Department of Pathology, Columbia University, New York, New York, USA.
Whittaker
Vaughn
V
Fan
Jianshe
J
Liu
Zhouru
Z
Manga
Kiran
K
Khan
Muzammil
M
Kontogianni
Katerina
K
Padmanabhan
Anand
A
Cohen
David
D
Suciu-Foca
Nicole
N
Ratner
Lloyd
L
Colovai
Adriana I
AI
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000961:Antilymphocyte Serum; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D000255:Adenosine Triphosphate; C512542:thymoglobulin