Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide.

Autor:	Vasudevan Nampoothiri R; The Ottawa Hospital Transplantation and Cellular Therapy Program, University of Ottawa, Ottawa, Ontario, Canada, rvasudevan@toh.ca., Avery L; Department of Biostatistics, University Health Network, University of Toronto, Toronto, Ontario, Canada., Pasic I; Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada., Prassas I; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada., Diamandis E; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.; Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada., Michelis FV; Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	Acta haematologica [Acta Haematol] 2024; Vol. 147 (5), pp. 511-524. Date of Electronic Publication: 2024 Feb 08.
DOI:	10.1159/000535706
Abstrakt:	Introduction: Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of established diagnostic protein biomarkers. Methods: Prospective samples were collected from patients with very severe SOS/VOD at diagnosis and days +3, +7, +14, and +30 post-initiation of defibrotide. Samples from age-matched controls with no VOD were collected at days +14, +30, +60, +90, and +180 following allogeneic HCT. Serum samples were analyzed for 2,925 protein levels by antibody-based proximity extension assay (PEA). Mean differences in the log-transformed abundance values were compared using t tests in a volcano plot. Results: Five patients with very severe SOS/VOD and 5 control patients were compared. Ten proteins were identified that showed a statistically significant and log-transformed 3-fold increase in concentration. They were CALCA, CCL20, GPR37, IGFBP4, IL1RL1, SLC39A14, SPINK4, FABP3, MYL3, and CHCHD10. Four different proteins, namely, CD83, leukocyte associated immunoglobulin-like receptor 2 (LAIR2), CD7, and HEM6 showed a significant decrease with defibrotide treatment. SOS/VOD resolved in 80% (n = 4) of patients, while 1 patient deceased due to SOS/VOD. Conclusion: PEA technology identified 10 proteins that were significantly elevated in patients with very severe SOS/VOD. Prospective studies in a larger cohort using this technology may be able to conclusively identify diagnostic protein biomarkers for SOS/VOD. (© 2024 S. Karger AG, Basel.)
Databáze:	MEDLINE
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