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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




TekijätAlexandersson Adam, Venäläinen Mikko S., Heikkilä Nelli, Huang Xiaobo, Taskinen Mervi, Huttunen Pasi, Elo Laura L., Koskenvuo Minna, Kekäläinen Eliisa

KustantajaJohn Wiley & Sons

Julkaisuvuosi2024

JournalImmunology and Cell Biology

Tietokannassa oleva lehden nimiImmunology and cell biology

Lehden akronyymiImmunol Cell Biol

Vuosikerta102

Numero6

Aloitussivu513

Lopetussivu525

ISSN0818-9641

eISSN1440-1711

DOIhttps://doi.org/10.1111/imcb.12762

Verkko-osoitehttps://onlinelibrary.wiley.com/doi/10.1111/imcb.12762

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/393536866


Tiivistelmä

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 [log2-fold change 1.5 (P = 0.00099), 2.5 (P = 0.00035) and 2.2 (P = 0.045) at time points 6, 12 and 24 months]. Flow cytometry confirmed that FCRL6 expression was higher in innate-like γδ T cells, indicating that these cells are involved in controlling CMV reactivation in HSCT recipients. In conclusion, the potentially druggable FCRL6 receptor on cytotoxic T cells appears to have a role in controlling CMV viremia after HSCT. Furthermore, our results suggest that system-level analysis is a useful addition to the studying of single biomarkers in allogenic HSCT.


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Last updated on 2024-26-11 at 18:24