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Open Access Research

Variability in CRP, regulatory T cells and effector T cells over time in gynaecological cancer patients: a study of potential oscillatory behaviour and correlations

Mutsa T Madondo1, Sandra Tuyaerts2, Brit B Turnbull3, Anke Vanderstraeten2, Holbrook Kohrt4, Balasubramanian Narasimhan3, Frederic Amant2, Michael Quinn5 and Magdalena Plebanski16*

Author Affiliations

1 Department of Immunology, Vaccine and Infectious Diseases Laboratory, Monash University, Melbourne, Australia

2 Division of Gynaecologic Oncology, Department of Oncology, KU Leuven, Leuven, Belgium

3 Department of Statistics and Department of Health Research and Policy, Stanford University, Stanford, CA, USA

4 Division of Haematology and Oncology, Centre for Clinical Sciences Research, Stanford University, Stanford, CA, USA

5 Womens Cancer Research Centre, Royal Women’s Hospital, Melbourne, Australia

6 Department of Immunology, Vaccine and Infectious Diseases Laboratory, School of Medicine and Health Science, Monash University Alfred Hospital Campus, 99 Commercial Road, Prahran, VIC 3181, Australia

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Journal of Translational Medicine 2014, 12:179  doi:10.1186/1479-5876-12-179

Published: 23 June 2014

Abstract

Background

The inflammatory marker, C reactive protein has been proposed to also be a biomarker for adaptive immune responses in cancer patients with a possible application in time based chemotherapy. Fluxes in serum CRP levels were suggested to be indicative of a cyclical process in which, immune activation is followed by auto-regulating immune suppression. The applicability of CRP as a biomarker for regulatory or effector T cells was therefore investigated in a cohort of patients with gynaecological malignancies.

Methods

Peripheral blood samples were obtained from a cohort of patients at 7 time points over a period of 12 days. Serum and mononuclear cells were isolated and CRP levels in serum were detected using ELISA while regulatory and effector T cell frequencies were assessed using flow cytometry. To test periodicity, periodogram analysis of data was employed while Pearson correlation and the Wilcoxon signed rank test were used to determine correlations.

Results

The statistical analysis used showed no evidence of periodic oscillation in either serum CRP concentrations or Teff and Treg frequencies. Furthermore, there was no apparent correlation between serum CRP concentrations and the corresponding frequencies of Tregs or Teffs. Relative to healthy individuals, the disease state in the patients neither significantly affected the mean frequency of Tregs nor the mean coefficient of variation within the Treg population over time. However, both Teff mean frequency and mean coefficient of variation were significantly reduced in patients.

Conclusion

Using our methods we were unable to detect CRP oscillations that could be used as a consistent serial biomarker for time based chemotherapy.

Keywords:
Inflammation; CRP; Gynaecological malignancies; Treg; Teff