Plasma proteomics reveals a low-expression immune phenotype in long-term pediatric hematopoietic cell transplantation survivors
Blood Immunology & Cellular Therapy, 2026
Wieringa N., Asbroek L., Müskens K., Mallée M., Koedijk I., te Pas B., de Koning C., Delemarre E., Kremer L., Bense J., de Pagter A., Lankester A., Lindemans C., Nierkens S., Pluijm S., Bresters D., Belderbos M.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Pathophysiology Patient Stratification | Plasma |  Olink Target 96 |
Abstract
Survival after pediatric allogeneic hematopoietic cell transplantation (HCT) has improved substantially. However, survivors remain at risk for late conditions, many of which may be influenced by immune and inflammatory alterations. The long-term immune landscape in pediatric HCT survivors remains poorly characterized.
We performed proximity extension assay-based profiling of 92 immune-related plasma proteins in 146 long-term survivors of childhood HCT and 22 controls. Clustering, differential expression and process analyses were performed to characterize immune profiles. Univariable and multivariable logistic regression models were used to identify associated clinical factors.
Unsupervised clustering identified two distinct immunoproteomic phenotypes among HCT survivors. Group A (n=53; 36%) displayed protein expression patterns comparable to controls, whereas Group B (n=93; 64%) showed lower immune-related protein expression than Group A and controls. Lower expression in Group B was observed across multiple biological processes, including lymphocyte interaction, neutrophil activation, and immune regulation. Group B was characterized by longer post-HCT follow-up (median 14.9 vs 8.2 years, p=0.02) and higher hematopoietic age (donor age at HCT plus follow-up; median 34.4 vs 26.4 years, p=0.03). In multivariable analysis, longer follow-up remained associated with the low-expression phenotype (Odds Ratio (OR): 1.92 per 10 years, p=0.05), while post-transplant cytomegalovirus reactivation was inversely associated (OR 0.32, p=0.04). No significant associations were observed with blood counts or clinical complications.
In conclusion, most long-term pediatric HCT survivors demonstrate a distinct low-expression immunoproteomic phenotype, associated with longer follow-up. These findings suggest alterations in post-transplant immune states, supporting prospective studies evaluating longitudinal dynamics and implications for long-term health.