Contemporary analysis of functional immune recovery to opportunistic and vaccine-preventable infections after allogeneic haemopoietic stem cell transplantation

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objectives: Infections are a major cause of mortality after allogeneic haemopoietic stem cell transplantation (alloHSCT), and immune recovery is necessary for prevention. Novel transplant procedures have changed the epidemiology of infections but contemporary data on functional immune recovery are limited. In this pilot study, we aimed to measure immune recovery in the current era of alloHSCT. Methods: Twenty, 13, 11, 9 and 9 alloHSCT recipients had blood collected at baseline (time of conditioning) and 3-, 6-, 9-, and 12-months post-alloHSCT, respectively. Clinical data were collected, and immune recovery was measured using immunophenotyping, lymphocyte proliferation, cytokine analysis and antibody isotyping. Results: Median absolute T- and B-cell counts were below normal from baseline until 9- to 12-months post-alloHSCT. Median absolute CD4+ T-cell counts recovered at 12-months post-alloHSCT. Positive proliferative responses to Aspergillus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), influenza and tetanus antigens were detected from 9 months. IL-6 was the most abundant cytokine in cell cultures. In cultures stimulated with CMV, EBV, influenza and tetanus peptides, the CD4+ T-cell count correlated with IL-1β (P = 0.045) and CD8+ T-cell count with IFNγ (P = 0.013) and IL-1β (P = 0.012). The NK-cell count correlated with IL-1β (P = 0.02) and IL-17a (P = 0.03). Median serum levels of IgG1, IgG2 and IgG3 were normal while IgG4 and IgA were below normal range throughout follow-up. Conclusions: This pilot study demonstrates that immune recovery can be measured using CD4+ T-cell counts, in vitro antigen stimulation and selected cytokines (IFNγ, IL-1β, IL-4, IL-6, IL-17, IL-21, IL-31) in alloHSCT recipients. While larger studies are required, monitoring immune recovery may have utility in predicting infection risk post-alloHSCT.

Original languageEnglish
Article numbere1040
Number of pages16
JournalClinical and Translational Immunology
Volume7
Issue number10
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • allogeneic
  • Aspergillus
  • cytokines
  • T-cell responses
  • vaccines

Cite this

@article{9a87a7ab01844c1d8ef15e4534666f12,
title = "Contemporary analysis of functional immune recovery to opportunistic and vaccine-preventable infections after allogeneic haemopoietic stem cell transplantation",
abstract = "Objectives: Infections are a major cause of mortality after allogeneic haemopoietic stem cell transplantation (alloHSCT), and immune recovery is necessary for prevention. Novel transplant procedures have changed the epidemiology of infections but contemporary data on functional immune recovery are limited. In this pilot study, we aimed to measure immune recovery in the current era of alloHSCT. Methods: Twenty, 13, 11, 9 and 9 alloHSCT recipients had blood collected at baseline (time of conditioning) and 3-, 6-, 9-, and 12-months post-alloHSCT, respectively. Clinical data were collected, and immune recovery was measured using immunophenotyping, lymphocyte proliferation, cytokine analysis and antibody isotyping. Results: Median absolute T- and B-cell counts were below normal from baseline until 9- to 12-months post-alloHSCT. Median absolute CD4+ T-cell counts recovered at 12-months post-alloHSCT. Positive proliferative responses to Aspergillus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), influenza and tetanus antigens were detected from 9 months. IL-6 was the most abundant cytokine in cell cultures. In cultures stimulated with CMV, EBV, influenza and tetanus peptides, the CD4+ T-cell count correlated with IL-1β (P = 0.045) and CD8+ T-cell count with IFNγ (P = 0.013) and IL-1β (P = 0.012). The NK-cell count correlated with IL-1β (P = 0.02) and IL-17a (P = 0.03). Median serum levels of IgG1, IgG2 and IgG3 were normal while IgG4 and IgA were below normal range throughout follow-up. Conclusions: This pilot study demonstrates that immune recovery can be measured using CD4+ T-cell counts, in vitro antigen stimulation and selected cytokines (IFNγ, IL-1β, IL-4, IL-6, IL-17, IL-21, IL-31) in alloHSCT recipients. While larger studies are required, monitoring immune recovery may have utility in predicting infection risk post-alloHSCT.",
keywords = "allogeneic, Aspergillus, cytokines, T-cell responses, vaccines",
author = "{De Silva}, Harini and Ffrench, {Rosemary Ann} and Maya Korem and Eva Orlowski-Oliver and Curtis, {David John} and Andrew Spencer and Sharon Avery and Sushrut Patil and Morrissey, {Catherine Orla}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/cti2.1040",
language = "English",
volume = "7",
journal = "Clinical and Translational Immunology",
issn = "2050-0068",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Contemporary analysis of functional immune recovery to opportunistic and vaccine-preventable infections after allogeneic haemopoietic stem cell transplantation

AU - De Silva, Harini

AU - Ffrench, Rosemary Ann

AU - Korem, Maya

AU - Orlowski-Oliver, Eva

AU - Curtis, David John

AU - Spencer, Andrew

AU - Avery, Sharon

AU - Patil, Sushrut

AU - Morrissey, Catherine Orla

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objectives: Infections are a major cause of mortality after allogeneic haemopoietic stem cell transplantation (alloHSCT), and immune recovery is necessary for prevention. Novel transplant procedures have changed the epidemiology of infections but contemporary data on functional immune recovery are limited. In this pilot study, we aimed to measure immune recovery in the current era of alloHSCT. Methods: Twenty, 13, 11, 9 and 9 alloHSCT recipients had blood collected at baseline (time of conditioning) and 3-, 6-, 9-, and 12-months post-alloHSCT, respectively. Clinical data were collected, and immune recovery was measured using immunophenotyping, lymphocyte proliferation, cytokine analysis and antibody isotyping. Results: Median absolute T- and B-cell counts were below normal from baseline until 9- to 12-months post-alloHSCT. Median absolute CD4+ T-cell counts recovered at 12-months post-alloHSCT. Positive proliferative responses to Aspergillus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), influenza and tetanus antigens were detected from 9 months. IL-6 was the most abundant cytokine in cell cultures. In cultures stimulated with CMV, EBV, influenza and tetanus peptides, the CD4+ T-cell count correlated with IL-1β (P = 0.045) and CD8+ T-cell count with IFNγ (P = 0.013) and IL-1β (P = 0.012). The NK-cell count correlated with IL-1β (P = 0.02) and IL-17a (P = 0.03). Median serum levels of IgG1, IgG2 and IgG3 were normal while IgG4 and IgA were below normal range throughout follow-up. Conclusions: This pilot study demonstrates that immune recovery can be measured using CD4+ T-cell counts, in vitro antigen stimulation and selected cytokines (IFNγ, IL-1β, IL-4, IL-6, IL-17, IL-21, IL-31) in alloHSCT recipients. While larger studies are required, monitoring immune recovery may have utility in predicting infection risk post-alloHSCT.

AB - Objectives: Infections are a major cause of mortality after allogeneic haemopoietic stem cell transplantation (alloHSCT), and immune recovery is necessary for prevention. Novel transplant procedures have changed the epidemiology of infections but contemporary data on functional immune recovery are limited. In this pilot study, we aimed to measure immune recovery in the current era of alloHSCT. Methods: Twenty, 13, 11, 9 and 9 alloHSCT recipients had blood collected at baseline (time of conditioning) and 3-, 6-, 9-, and 12-months post-alloHSCT, respectively. Clinical data were collected, and immune recovery was measured using immunophenotyping, lymphocyte proliferation, cytokine analysis and antibody isotyping. Results: Median absolute T- and B-cell counts were below normal from baseline until 9- to 12-months post-alloHSCT. Median absolute CD4+ T-cell counts recovered at 12-months post-alloHSCT. Positive proliferative responses to Aspergillus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), influenza and tetanus antigens were detected from 9 months. IL-6 was the most abundant cytokine in cell cultures. In cultures stimulated with CMV, EBV, influenza and tetanus peptides, the CD4+ T-cell count correlated with IL-1β (P = 0.045) and CD8+ T-cell count with IFNγ (P = 0.013) and IL-1β (P = 0.012). The NK-cell count correlated with IL-1β (P = 0.02) and IL-17a (P = 0.03). Median serum levels of IgG1, IgG2 and IgG3 were normal while IgG4 and IgA were below normal range throughout follow-up. Conclusions: This pilot study demonstrates that immune recovery can be measured using CD4+ T-cell counts, in vitro antigen stimulation and selected cytokines (IFNγ, IL-1β, IL-4, IL-6, IL-17, IL-21, IL-31) in alloHSCT recipients. While larger studies are required, monitoring immune recovery may have utility in predicting infection risk post-alloHSCT.

KW - allogeneic

KW - Aspergillus

KW - cytokines

KW - T-cell responses

KW - vaccines

UR - http://www.scopus.com/inward/record.url?scp=85055346020&partnerID=8YFLogxK

U2 - 10.1002/cti2.1040

DO - 10.1002/cti2.1040

M3 - Article

VL - 7

JO - Clinical and Translational Immunology

JF - Clinical and Translational Immunology

SN - 2050-0068

IS - 10

M1 - e1040

ER -