Open Access Highly Accessed Research article

A specific immune transcriptomic profile discriminates chronic kidney disease patients in predialysis from hemodialyzed patients

Gianluigi Zaza1*, Simona Granata1, Federica Rascio2, Paola Pontrelli2, Maria Pia Dell’Oglio2, Sharon Natasha Cox2, Giovanni Pertosa2, Giuseppe Grandaliano3 and Antonio Lupo1

Author Affiliations

1 Renal Unit, Department of Medicine, University-Hospital of Verona, Piazzale A. Stefani 1, Verona 37126, Italy

2 Renal, Dialysis and Transplant Unit-Department of Emergency and Transplantation, University of Bari, Piazza Giulio Cesare 1, Bari 70124, Italy

3 Department of Medical and Surgical Sciences, University of Foggia, Via Pinto, 1, Foggia 71100, Italy

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BMC Medical Genomics 2013, 6:17  doi:10.1186/1755-8794-6-17

Published: 10 May 2013

Abstract

Background

Chronic kidney disease (CKD) patients present a complex interaction between the innate and adaptive immune systems, in which immune activation (hypercytokinemia and acute-phase response) and immune suppression (impairment of response to infections and poor development of adaptive immunity) coexist. In this setting, circulating uremic toxins and microinflammation play a critical role. This condition, already present in the last stages of renal damage, seems to be enhanced by the contact of blood with bioincompatible extracorporeal hemodialysis (HD) devices. However, although largely described, the cellular machinery associated to the CKD- and HD-related immune-dysfunction is still poorly defined. Understanding the mechanisms behind this important complication may generate a perspective for improving patients outcome.

Methods

To better recognize the biological bases of the CKD-related immune dysfunction and to identify differences between CKD patients in conservative (CKD) from those in HD treatment, we used an high-throughput strategy (microarray) combined with classical bio-molecular approaches.

Results

Immune transcriptomic screening of peripheral blood mononuclear cells (1030 gene probe sets selected by Gene-Ontology) showed that 275 gene probe sets (corresponding to 213 genes) discriminated 9 CKD patients stage III-IV (mean ± SD of eGFR: 32.27±14.7 ml/min) from 17 HD patients (p < 0.0001, FDR = 5%). Seventy-one genes were up- and 142 down-regulated in HD patients. Functional analysis revealed, then, close biological links among the selected genes with a pivotal role of PTX3, IL-15 (up-regulated in HD) and HLA-G (down-regulated in HD). ELISA, performed on an independent testing-group [11 CKD stage III-IV (mean ± SD of eGFR: 30.26±14.89 ml/min) and 13 HD] confirmed that HLA-G, a protein with inhibition effects on several immunological cell lines including natural killers (NK), was down-expressed in HD (p = 0.04). Additionally, in the testing-group, protein levels of CX3CR1, an highly selective chemokine receptor and surface marker for cytotoxic effector lymphocytes, resulted higher expressed in HD compared to CKD (p < 0.01).

Conclusion

Taken together our results show, for the first time, that HD patients present a different immune-pattern compared to the un-dialyzed CKD patients. Among the selected genes, some of them encode for important biological elements involved in proliferation/activation of cytotoxic effector lymphocytes and in the immune-inflammatory cellular machinery. Additionally, this study reveals new potential diagnostic bio-markers and therapeutic targets.