The number of FoxP3 regulatory T cells in the circulation may be a predictive biomarker for kidney transplant recipients: A multistage systematic review.

BACKGROUND: The kinetics of the FoxP3 regulatory T-cell (Treg) population in kidney transplant recipients (KTR) are related to the clinical effect of immunosuppression based on mammalian Target Of Rapamycin inhibitors (mTORi) with/without belatacept (predictive biomarker). METHODS: A multistage systematic review of published and unpublished literature is presented [registration IDs in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42017057570, CRD42018085019, CRD42018084941, CRD42018085186]. A multidisciplinary supervision mechanism for contextualizing of search findings was required. The peripheral blood immune cell phenotypes encompassing all regulatory cells in KTRs were assessed in order to suggest new markers of acute rejection-associated acute allograft dysfunction (AR/AAD) events in KTRs treated with mTORi alone or combined to belatacept. Quantitative estimates and evaluation of the body of evidence are provided. RESULTS: An increase in Tregs and other regulatory cell types in the circulation in KTRs under mTORi with/without belatacept were observed. Patients with increased Tregs presented a low frequency of AR/AAD events compared to those in which the number of Tregs remained unchanged or even diminished [Odds Ratio (OR)/95% confidence interval (95% CI)/I2/number of studies (n): 0.31/0.10-0.93/0%/6]. Nevertheless, there are too few trials to consider Tregs in the circulation as a predictive biomarker. Inadequate reporting prevents appreciating clinical relevance in such studies. CONCLUSIONS: Despite advances, clinical qualification of potential predictive biomarkers continues to be difficult. Clinical evidence on Tregs in KTRs needs to be enlarged. Biomarkers should be able to evaluate the effect of medicines targeted to specific patient populations.

Data on a new biomarker for kidney transplant recipients: The number of FoxP3 regulatory T cells in the circulation.

This article presents unrevealed details of the systematic review process of the article "The number of FoxP3 regulatory T cells in the circulation may be a predictive biomarker for kidney transplant recipients: A multistage systematic review" (Herrera-Gómez et al., 2018). Eligibility criteria guiding searches and study selection, the risk of bias assessment, the assessment of medicine-test codependency (evaluation of the body of evidence), and meta-analytic calculations are provided. The data allows other researchers, particularly those involved in experiments on Translational Epidemiology applied to Pharmacology, to corroborate and extend our assessments.

Peripheral blood regulatory T cell counts as a predictive biomarker for the outcome of kidney transplant: A systematic review. / Recuentos de células T reguladoras en sangre periférica como biomarcador predictivo del resultado del trasplante renal: revisión sistemática.

BACKGROUND AND OBJECTIVE: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. MATERIAL AND METHODS: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. RESULTS: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. CONCLUSIONS: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function. REGISTRATION: PROSPERO (CRD42016046285).