Diagnostic and Predictive Value of an Immune Monitoring Program for Complications after Kidney Transplantation

Abstract β-1,4-mannosylglycoprotein 4-β-N-acetylglucosaminyltransferase (MGAT3) is a key molecule for the innate immune system. We tested the hypothesis that intronic antisense long non-coding RNA, MGAT3-AS1, can predict delayed allograft function after kidney transplantation. We prospectively assessed kidney function and MGAT3-AS1 in 129 incident deceased donor kidney transplant recipients before and after transplantation. MGAT3-AS1 levels were measured in mononuclear cells using qRT-PCR. Delayed graft function was defined by at least one dialysis session within 7 days of transplantation. Delayed graft function occurred in 22 out of 129 transplant recipients (17%). Median MGAT3-AS1 after transplantation was significantly lower in patients with delayed graft function compared to patients with immediate graft function (6.5 × 10−6, IQR 3.0 × 10−6 to 8.4 × 10−6; vs. 8.3 × 10−6, IQR 5.0 × 10−6 to 12.8 × 10−6; p < 0.05). The median preoperative MGAT3-AS1 was significantly lower in kidney recipients with delayed graft function (5.1 × 10−6, IQR, 2.4 × 10−6 to 6.8 × 10−6) compared to recipients with immediate graft function (8.9 × 10−6, IQR, 6.8 × 10−6 to 13.4 × 10−6; p < 0.05). Receiver-operator characteristics showed that preoperative MGAT3-AS1 predicted delayed graft function (area under curve, 0.83; 95% CI, 0.65 to 1.00; p < 0.01). We observed a positive predictive value of 0.57, and a negative predictive value of 0.95. Long non-coding RNA, MGAT3-AS1, indicates short-term outcome in patients with deceased donor kidney transplantation.

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Laboratory Accuracy Improvement in the UK NEQAS Leucocyte Immunophenotyping Immune Monitoring Program: An Eleven-Year Review via Longitudinal Mixed Effects Modeling

Cytometry Part B Clinical Cytometry ◽

10.1002/cyto.b.21531 ◽

2017 ◽

Vol 94 (2) ◽

pp. 250-256 ◽

Cited By ~ 6

Author(s):

John Bainbridge ◽

Wes Rountree ◽

Raul Louzao ◽

John Wong ◽

Liam Whitby ◽

...

Keyword(s):

Monitoring Program ◽

Immune Monitoring ◽

Mixed Effects ◽

Accuracy Improvement ◽

Mixed Effects Modeling ◽

The Uk

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Prospect: A randomized, double-blind, phase III efficacy trial of PROSTVAC.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.tps4699 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. TPS4699-TPS4699

Author(s):

Olga Bandman ◽

Alain Delcayre ◽

Reiner Laus ◽

Wayne Russell Godfrey ◽

Philip W. Kantoff ◽

...

Keyword(s):

Immune System ◽

Phase Ii ◽

Phase Ii Trial ◽

Monitoring Program ◽

Immune Monitoring ◽

Phase Iii ◽

System Response ◽

Double Blind ◽

Androgen Ablation ◽

T Cell Subpopulations

TPS4699 Background: PROSTVAC is a candidate cancer vaccine comprised of two recombinant poxviral vectors: vaccinia (V) and fowlpox (F), each with insertions of four human genes: PSA and three costimulatory molecules (TRICOM) - LFA-3, B7.1 and ICAM-1. This off the shelf vaccine demonstrated a statistically significant overall survival (OS) benefit of 8.5 months while displaying a favorable side effect profile in patients (pts) with asymptomatic to minimally symptomatic prostate cancer (mCRPC) in a randomized, placebo –controlled 122-pt Phase II trial. Data from this Phase II trial supported the design of a Phase III protocol that will rigorously test the hypothesis of OS benefit, as well as expand our understanding of immune system response to cancer vaccines. Methods: 1200 pts will be randomized in a double-blind fashion to three arms: PROSTVAC, PROSTVAC+GM-CSF, or Placebo, at 1:1:1 ratio. A five-month treatment regimen will include a priming vaccination with PROSTVAC-V, and six booster vaccinations with PROSTVAC-F. Eligible pts will have asymptomatic or minimally symptomatic mCRPC, and progression despite androgen ablation and be chemotherapy-naïve. Pts with rapidly progressing disease will be excluded, as well as pts with risk factors for developing vaccinia-associated complications. The projected trial size is 400 pts per arm for at least 85% power. Primary endpoint is OS. The final analyses will be event-driven and will compare each active arm independently with placebo. Pts will be followed for 12 months after the projected number of events in each arm is realized. Secondary endpoint is proportion of event-free pts at 6 months compared to placebo. A number of exploratory endpoints are planned, including immune response to immunizing antigen, non-vaccine-contained prostate antigens, tumor-associated antigens; changes in baseline biomarker levels and CTC levels, as well as characterization of T cell subpopulations. The thorough immune monitoring program would provide basis for future studies on the effects of cancer immunotherapy on immune system and facilitate search for potential biomarkers of such effects. The trial is currently open for enrollment. ClinicalTrials.gov registry number: NCT00450463.

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