Skip to main content
Erschienen in: International Journal of Hematology 3/2023

22.07.2023 | Original Article

Plasma ubiquitin C-terminal hydrolase-L1 (UCH-L1) level as a blood biomarker of neurological damage after allogeneic hematopoietic cell transplantation

verfasst von: Yosuke Okada, Hideki Nakasone, Kazuki Yoshimura, Masaharu Tamaki, Machiko Kusuda, Yuhei Nakamura, Masakatsu Kawamura, Shunto Kawamura, Junko Takeshita, Nozomu Yoshino, Yukiko Misaki, Ayumi Gomyo, Aki Tanihara, Shun-ichi Kimura, Shinichi Kako, Yoshinobu Kanda

Erschienen in: International Journal of Hematology | Ausgabe 3/2023

Einloggen, um Zugang zu erhalten

Abstract

Several biofluid-based biomarkers for traumatic brain injury show promise for use in diagnosis and outcome prediction. In contrast, few studies have investigated biomarkers for non-traumatic brain injury. We focused on ubiquitin C-terminal hydrolase-L1 (UCH-L1), which has been proposed as a screening tool for traumatic brain injury, and investigated whether the plasma UCH-L1 level could also be a useful biomarker in patients with non-traumatic brain injury. We measured UCH-L1 in 25 patients who had experienced neurological complications after allogeneic hematopoietic cell transplantation (HCT) and 22 control patients without any complications or graft-versus-host disease. Although UCH-L1 levels before HCT did not differ significantly (P = 0.053), levels after HCT were higher in patients with neurological complications compared with the control group (P < 0.001). At a UCH-L1 cutoff value of 0.072 ng/ml, sensitivity was 68.0% and specificity was 100%. The statistical power of UCH-L1 for neurological complications seemed to be higher than that of CT and comparable to that of MRI. Thus, increased levels of UCH-L1 might reflect the presence of neurological damage even in patients with non-traumatic brain injury. Further large cohort investigations are warranted.
Literatur
1.
Zurück zum Zitat Erkkinen MG, Berkowitz AL. A clinical approach to diagnosing encephalopathy. Am J Med. 2019;132(10):1142–7.CrossRefPubMed Erkkinen MG, Berkowitz AL. A clinical approach to diagnosing encephalopathy. Am J Med. 2019;132(10):1142–7.CrossRefPubMed
2.
Zurück zum Zitat Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, et al. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018;18(2):165–80.CrossRefPubMedPubMedCentral Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, et al. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018;18(2):165–80.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Ebner F, Moseby-Knappe M, Mattsson-Carlgren N, Lilja G, Dragancea I, Undén J, et al. Serum GFAP and UCH-L1 for the prediction of neurological outcome in comatose cardiac arrest patients. Resusc. 2020;154:61–8. Ebner F, Moseby-Knappe M, Mattsson-Carlgren N, Lilja G, Dragancea I, Undén J, et al. Serum GFAP and UCH-L1 for the prediction of neurological outcome in comatose cardiac arrest patients. Resusc. 2020;154:61–8.
4.
Zurück zum Zitat Bishop P, Rocca D, Henley JM. Ubiquitin C-terminal hydrolase L1 (UCH-L1): structure, distribution and roles in brain function and dysfunction. Biochem J. 2016;473(16):2453–62.CrossRefPubMed Bishop P, Rocca D, Henley JM. Ubiquitin C-terminal hydrolase L1 (UCH-L1): structure, distribution and roles in brain function and dysfunction. Biochem J. 2016;473(16):2453–62.CrossRefPubMed
5.
Zurück zum Zitat Doran JF, Jackson P, Kynoch PA, Thompson RJ. Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis. J Neurochem. 1983;40(6):1542–7.CrossRefPubMed Doran JF, Jackson P, Kynoch PA, Thompson RJ. Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis. J Neurochem. 1983;40(6):1542–7.CrossRefPubMed
6.
Zurück zum Zitat Amoo M, Henry J, O’Halloran PJ, Brennan P, Husien MB, Campbell M, et al. S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy. Neurosurg Rev. 2022;45(2):1171–93.CrossRefPubMed Amoo M, Henry J, O’Halloran PJ, Brennan P, Husien MB, Campbell M, et al. S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy. Neurosurg Rev. 2022;45(2):1171–93.CrossRefPubMed
7.
Zurück zum Zitat Korley FK, Jain S, Sun X, Puccio AM, Yue JK, Gardner RC, et al. Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: an observational cohort study. Lancet Neurol. 2022;21(9):803–13.CrossRefPubMed Korley FK, Jain S, Sun X, Puccio AM, Yue JK, Gardner RC, et al. Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: an observational cohort study. Lancet Neurol. 2022;21(9):803–13.CrossRefPubMed
8.
Zurück zum Zitat Papa L, Zonfrillo MR, Welch RD, Lewis LM, Braga CF, Tan CN, et al. Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: a prospective cohort study. BMJ Paediatr Open. 2019;3(1): e000473.CrossRefPubMedPubMedCentral Papa L, Zonfrillo MR, Welch RD, Lewis LM, Braga CF, Tan CN, et al. Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: a prospective cohort study. BMJ Paediatr Open. 2019;3(1): e000473.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Syed FI, Couriel DR, Frame D, Srinivasan A. Central nervous system complications of hematopoietic stem cell transplant. Hematol Oncol Clin North Am. 2016;30(4):887–98.CrossRefPubMed Syed FI, Couriel DR, Frame D, Srinivasan A. Central nervous system complications of hematopoietic stem cell transplant. Hematol Oncol Clin North Am. 2016;30(4):887–98.CrossRefPubMed
10.
Zurück zum Zitat Curtis RE, Travis LB, Rowlings PA, Socié G, Kingma DW, Banks PM, et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood. 1999;94(7):2208–16.PubMed Curtis RE, Travis LB, Rowlings PA, Socié G, Kingma DW, Banks PM, et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood. 1999;94(7):2208–16.PubMed
11.
Zurück zum Zitat Beitinjaneh A, McKinney AM, Cao Q, Weisdorf DJ. Toxic leukoencephalopathy following fludarabine-associated hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2011;17(3):300–8.CrossRef Beitinjaneh A, McKinney AM, Cao Q, Weisdorf DJ. Toxic leukoencephalopathy following fludarabine-associated hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2011;17(3):300–8.CrossRef
12.
Zurück zum Zitat Caselli D, Rosati A, Faraci M, Podda M, Ripaldi M, Longoni D, et al. Risk of seizures in children receiving busulphan-containing regimens for stem cell transplantation. Biol Blood Marrow Transpl. 2014;20(2):282–5.CrossRef Caselli D, Rosati A, Faraci M, Podda M, Ripaldi M, Longoni D, et al. Risk of seizures in children receiving busulphan-containing regimens for stem cell transplantation. Biol Blood Marrow Transpl. 2014;20(2):282–5.CrossRef
13.
Zurück zum Zitat Bhatt VR, Balasetti V, Jasem JA, Giri S, Armitage JO, Loberiza FR, et al. Central nervous system complications and outcomes after allogeneic hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk. 2015;15(10):606–11.CrossRefPubMed Bhatt VR, Balasetti V, Jasem JA, Giri S, Armitage JO, Loberiza FR, et al. Central nervous system complications and outcomes after allogeneic hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk. 2015;15(10):606–11.CrossRefPubMed
14.
Zurück zum Zitat Maffini E, Festuccia M, Brunello L, Boccadoro M, Giaccone L, Bruno B. Neurologic complications after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2017;23(3):388–97.CrossRef Maffini E, Festuccia M, Brunello L, Boccadoro M, Giaccone L, Bruno B. Neurologic complications after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2017;23(3):388–97.CrossRef
15.
Zurück zum Zitat Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.CrossRefPubMed Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.CrossRefPubMed
16.
Zurück zum Zitat Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J. PGP 9.5–a new marker for vertebrate neurons and neuroendocrine cells. Brain Res. 1983;278(1–2):224–8.CrossRefPubMed Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J. PGP 9.5–a new marker for vertebrate neurons and neuroendocrine cells. Brain Res. 1983;278(1–2):224–8.CrossRefPubMed
17.
Zurück zum Zitat Thelin EP, Zeiler FA, Ercole A, Mondello S, Büki A, Bellander BM, et al. Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics: a systematic review. Front Neurol. 2017;8:300.CrossRefPubMedPubMedCentral Thelin EP, Zeiler FA, Ercole A, Mondello S, Büki A, Bellander BM, et al. Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics: a systematic review. Front Neurol. 2017;8:300.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Liu H, Povysheva N, Rose ME, Mi Z, Banton JS, Li W, et al. Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia. Proc Natl Acad Sci USA. 2019;116(10):4643–50.CrossRefPubMedPubMedCentral Liu H, Povysheva N, Rose ME, Mi Z, Banton JS, Li W, et al. Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia. Proc Natl Acad Sci USA. 2019;116(10):4643–50.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Papa L, Brophy GM, Welch RD, Lewis LM, Braga CF, Tan CN, et al. Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA Neurol. 2016;73(5):551–60.CrossRefPubMedPubMedCentral Papa L, Brophy GM, Welch RD, Lewis LM, Braga CF, Tan CN, et al. Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA Neurol. 2016;73(5):551–60.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Brophy GM, Mondello S, Papa L, Robicsek SA, Gabrielli A, Tepas J, et al. Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids. J Neurotrauma. 2011;28(6):861–70.CrossRefPubMedPubMedCentral Brophy GM, Mondello S, Papa L, Robicsek SA, Gabrielli A, Tepas J, et al. Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids. J Neurotrauma. 2011;28(6):861–70.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Blyth BJ, Farahvar A, He H, Nayak A, Yang C, Shaw G, et al. Elevated serum ubiquitin carboxy-terminal hydrolase L1 is associated with abnormal blood-brain barrier function after traumatic brain injury. J Neurotrauma. 2011;28(12):2453–62.CrossRefPubMed Blyth BJ, Farahvar A, He H, Nayak A, Yang C, Shaw G, et al. Elevated serum ubiquitin carboxy-terminal hydrolase L1 is associated with abnormal blood-brain barrier function after traumatic brain injury. J Neurotrauma. 2011;28(12):2453–62.CrossRefPubMed
22.
Zurück zum Zitat Bazarian JJ, Biberthaler P, Welch RD, Lewis LM, Barzo P, Bogner-Flatz V, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17(9):782–9.CrossRefPubMed Bazarian JJ, Biberthaler P, Welch RD, Lewis LM, Barzo P, Bogner-Flatz V, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17(9):782–9.CrossRefPubMed
23.
Zurück zum Zitat Czeiter E, Amrein K, Gravesteijn BY, Lecky F, Menon DK, Mondello S, et al. Blood biomarkers on admission in acute traumatic brain injury: relations to severity, CT findings and care path in the CENTER-TBI study. EBioMed. 2020;56: 102785.CrossRef Czeiter E, Amrein K, Gravesteijn BY, Lecky F, Menon DK, Mondello S, et al. Blood biomarkers on admission in acute traumatic brain injury: relations to severity, CT findings and care path in the CENTER-TBI study. EBioMed. 2020;56: 102785.CrossRef
24.
Zurück zum Zitat Kurihara LJ, Kikuchi T, Wada K, Tilghman SM. Loss of Uch-L1 and Uch-L3 leads to neurodegeneration, posterior paralysis and dysphagia. Hum Mol Genet. 2001;10(18):1963–70.CrossRefPubMed Kurihara LJ, Kikuchi T, Wada K, Tilghman SM. Loss of Uch-L1 and Uch-L3 leads to neurodegeneration, posterior paralysis and dysphagia. Hum Mol Genet. 2001;10(18):1963–70.CrossRefPubMed
25.
Zurück zum Zitat Osaka H, Wang YL, Takada K, Takizawa S, Setsuie R, Li H, et al. Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Hum Mol Genet. 2003;12(16):1945–58.CrossRefPubMed Osaka H, Wang YL, Takada K, Takizawa S, Setsuie R, Li H, et al. Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Hum Mol Genet. 2003;12(16):1945–58.CrossRefPubMed
26.
Zurück zum Zitat George JN, Selby GB. Thrombotic microangiopathy after allogeneic bone marrow transplantation: a pathologic abnormality associated with diverse clinical syndromes. Bone Marrow Transpl. 2004;33(11):1073–4.CrossRef George JN, Selby GB. Thrombotic microangiopathy after allogeneic bone marrow transplantation: a pathologic abnormality associated with diverse clinical syndromes. Bone Marrow Transpl. 2004;33(11):1073–4.CrossRef
27.
28.
Metadaten
Titel
Plasma ubiquitin C-terminal hydrolase-L1 (UCH-L1) level as a blood biomarker of neurological damage after allogeneic hematopoietic cell transplantation
verfasst von
Yosuke Okada
Hideki Nakasone
Kazuki Yoshimura
Masaharu Tamaki
Machiko Kusuda
Yuhei Nakamura
Masakatsu Kawamura
Shunto Kawamura
Junko Takeshita
Nozomu Yoshino
Yukiko Misaki
Ayumi Gomyo
Aki Tanihara
Shun-ichi Kimura
Shinichi Kako
Yoshinobu Kanda
Publikationsdatum
22.07.2023
Verlag
Springer Nature Singapore
Erschienen in
International Journal of Hematology / Ausgabe 3/2023
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-023-03642-7

Weitere Artikel der Ausgabe 3/2023

International Journal of Hematology 3/2023 Zur Ausgabe

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Das sind die führenden Symptome junger Darmkrebspatienten

Darmkrebserkrankungen in jüngeren Jahren sind ein zunehmendes Problem, das häufig längere Zeit übersehen wird, gerade weil die Patienten noch nicht alt sind. Welche Anzeichen Ärzte stutzig machen sollten, hat eine Metaanalyse herausgearbeitet.

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.