Proteomics screening after pediatric allogenic hematopoietic stem cell transplantation reveals an association between increased expression of inhibitory receptor FCRL6 on γδ T cells and cytomegalovirus reactivation.
FCRL6
HSCT
biomarkers
gd T cells
pediatric
proteomics
γδ T cells
Journal
Immunology and cell biology
ISSN: 1440-1711
Titre abrégé: Immunol Cell Biol
Pays: United States
ID NLM: 8706300
Informations de publication
Date de publication:
10 May 2024
10 May 2024
Historique:
revised:
07
04
2024
revised:
10
04
2024
received:
23
11
2023
accepted:
10
04
2024
medline:
10
5
2024
pubmed:
10
5
2024
entrez:
10
5
2024
Statut:
aheadofprint
Résumé
We studied the associations between inflammation-related proteins in circulation and complications after pediatric allogenic hematopoietic stem cell transplantation (HSCT), to reveal proteomic signatures or individual soluble proteins associated with specific complications after HSCT. We used a proteomics method called Proximity Extension Assay to repeatedly measure 180 different proteins together with clinical variables, cellular immune reconstitution and blood viral copy numbers in 27 children (1-18 years of age) during a 2-year follow-up after allogenic HSCT. Protein profile analysis was performed using unsupervised hierarchical clustering and a regression-based method, while the Bonferroni-corrected Mann-Whitney U-test was used for time point-specific comparison of individual proteins against outcome. At 6 months after allogenic HSCT, we could identify a protein profile pattern associated with occurrence of the complications such as chronic graft-versus-host disease, viral infections, relapse and death. When protein markers were analyzed separately, the plasma concentration of the inhibitory and cytotoxic T-cell surface protein FCRL6 (Fc receptor-like 6) was higher in patients with cytomegalovirus (CMV) viremia [log
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Research Council
Pays : International
Informations de copyright
© 2024 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.
Références
Wingard JR, Majhail NS, Brazauskas R, et al. Long‐term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol 2011; 29: 2230–2239.
Adom D, Rowan C, Adeniyan T, Yang J, Paczesny S. Biomarkers for allogeneic HCT outcomes. Front Immunol 2020; 11: 673.
de Koning C, Plantinga M, Besseling P, Boelens JJ, Nierkens S. Immune reconstitution after allogeneic hematopoietic cell transplantation in children. Biol Blood Marrow Transplant 2016; 22: 195–206.
Blennow O, Ljungman P, Sparrelid E, Mattsson J, Remberger M. Incidence, risk factors, and outcome of bloodstream infections during the pre‐engraftment phase in 521 allogeneic hematopoietic stem cell transplantations. Transpl Infect Dis 2014; 16: 106–114.
Zhang P, Jiang EL, Yang DL, et al. Risk factors and prognosis of invasive fungal infections in allogeneic stem cell transplantation recipients: a single‐institution experience. Transpl Infect Dis 2010; 12: 316–321.
Haidar G, Boeckh M, Singh N. Cytomegalovirus infection in solid organ and hematopoietic cell transplantation: state of the evidence. J Infect Dis 2020; 221: S23–S31.
Gottlieb DJ, Clancy LE, Withers B, et al. Prophylactic antigen‐specific T‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant. Clin Transl Immunology 2021; 10: e1249.
Greenberg PD, Reusser P, Goodrich JM, Riddell SR. Development of a treatment regimen for human cytomegalovirus (CMV) infection in bone marrow transplantation recipients by adoptive transfer of donor‐derived CMV‐specific T cell clones expanded in vitro. Ann N Y Acad Sci 1991; 636: 184–195.
Shafat MS, Mehra V, Peggs KS, Roddie C. Cellular therapeutic approaches to cytomegalovirus infection following allogeneic stem cell transplantation. Front Immunol 2020; 11: 1694.
Stern L, Withers B, Avdic S, et al. Human cytomegalovirus latency and reactivation in allogeneic hematopoietic stem cell transplant recipients. Front Microbiol 2019; 10: 1186.
Camargo JF, Wieder ED, Kimble E, et al. Deep functional immunophenotyping predicts risk of cytomegalovirus reactivation after hematopoietic cell transplantation. Blood 2019; 133: 867–877.
Chen S, Zeiser R. Novel biomarkers for outcome after allogeneic hematopoietic stem cell transplantation. Front Immunol 2020; 11: 1854.
Giaccone L, Faraci DG, Butera S, et al. Biomarkers for acute and chronic graft versus host disease: state of the art. Expert Rev Hematol 2021; 14: 79–96.
Davis MM. Systems immunology. Curr Opin Immunol 2020; 65: 79–82.
Alexandersson A, Koskenvuo M, Tiderman A, et al. Viral infections and immune reconstitution interaction after pediatric allogenic hematopoietic stem cell transplantation. Infect Dis 2019; 51: 772–778.
Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci 2006; 11: 529–543.
Wang YD, Yan PY. Expression of matrix metalloproteinase‐1 and tissue inhibitor of metalloproteinase‐1 in ulcerative colitis. World J Gastroenterol 2006; 12: 6050–6053.
Montaño M, Sansores RH, Becerril C, et al. FEV1 inversely correlates with metalloproteinases 1, 7, 9 and CRP in COPD by biomass smoke exposure. Respir Res 2014; 15: 74.
Rumbaugh J, Turchan‐Cholewo J, Galey D, et al. Interaction of HIV tat and matrix metalloproteinase in HIV neuropathogenesis: a new host defense mechanism. FASEB J 2006; 20: 1736–1738.
Uhlén M, Karlsson MJ, Hober A, et al. The human secretome. Sci Signal 2019; 12: eaaz0274.
Holtan SG, DeFor TE, Panoskaltsis‐Mortari A, et al. Amphiregulin modifies the Minnesota acute graft‐versus‐host disease risk score: results from BMT CTN 0302/0802. Blood Adv 2018; 2: 1882–1888.
Holtan SG, Khera N, Levine JE, et al. Late acute graft‐versus‐host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors. Blood 2016; 128: 2350–2358.
Schreeder DM, Cannon JP, Wu J, Li R, Shakhmatov MA, Davis RS. Cutting edge: FcR‐like 6 is an MHC class II receptor. J Immunol 2010; 185: 23–27.
Kulemzin SV, Zamoshnikova AY, Yurchenko MY, et al. FCRL6 receptor: expression and associated proteins. Immunol Lett 2011; 134: 174–182.
Davis RS. Roles for the FCRL6 immunoreceptor in tumor immunology. Front Immunol 2020; 11: 575175.
Johnson DB, Nixon MJ, Wang Y, et al. Tumor‐specific MHC‐II expression drives a unique pattern of resistance to immunotherapy via LAG‐3/FCRL6 engagement. JCI Insight 2018; 3: e120360.
Schreeder DM, Pan J, Li FJ, Vivier E, Davis RS. FCRL6 distinguishes mature cytotoxic lymphocytes and is upregulated in patients with B‐cell chronic lymphocytic leukemia. Eur J Immunol 2008; 38: 3159–3166.
Wilson TJ, Presti RM, Tassi I, Overton ET, Cella M, Colonna M. FcRL6, a new ITIM‐bearing receptor on cytolytic cells, is broadly expressed by lymphocytes following HIV‐1 infection. Blood 2007; 109: 3786–3793.
Arruda LCM, Gaballa A, Uhlin M. Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta‐analysis. Blood Adv 2019; 3: 3436–3448.
Park M, Im HJ, Lee YJ, et al. Reconstitution of T and NK cells after haploidentical hematopoietic cell transplantation using αβ T cell‐depleted grafts and the clinical implication of γδ T cells. Clin Transpl 2018; 32: e13147.
Gaballa A, Stikvoort A, Önfelt B, et al. T‐cell frequencies of CD8+γδ and CD27+γδ cells in the stem cell graft predict the outcome after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2019; 54: 1562–1574.
Prinz I, Koenecke C. Antigen‐specific γδ T cells contribute to cytomegalovirus control after stem cell transplantation. Curr Opin Immunol 2023; 82: 102303.
Deseke M, Rampoldi F, Sandrock I, et al. A CMV‐induced adaptive human Vδ1+γδ T cell clone recognizes HLA‐DR. J Exp Med 2022; 219: e20212525.
Handgretinger R, Schilbach K. The potential role of γδ T cells after allogeneic HCT for leukemia. Blood 2018; 131: 1063–1072.
Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft‐versus‐host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant 2015; 21: 389–401.
Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft‐versus‐host disease in human recipients of marrow from HL‐A‐matched sibling donors. Transplantation 1974; 18: 295–304.
Assarsson E, Lundberg M, Holmquist G, et al. Homogenous 96‐plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS One 2014; 9: e95192.
Assarsson E, Lundberg M. Development and Validation of Customized PEA Biomarker Panels with Clinical Utility, in Advancing Precision Medicine: Current and Future Proteogenomic Strategies for Biomarker Discovery and Development. Washington, DC: Science/AAAS; 2017:32–36.
Conesa A, Nueda MJ, Ferrer A, Talón M. maSigPro: a method to identify significantly differential expression profiles in time‐course microarray experiments. Bioinformatics 2006; 22: 1096–1102.