Cognitive impairments correlate with increased central nervous system immune activation after allogeneic haematopoietic stem cell transplantation.
Erik BobergNadir KadriDaniel W HageyLilly SchwielerSamir El AndaloussiSophie ErhardtEllen IacobaeusKatarina Le BlancPublished in: Leukemia (2023)
Murine studies indicate that, after allogeneic haematopoietic stem cell transplantation (aHSCT), donor-derived macrophages replace damaged microglia and alloreactive T-cells invade the central nervous system (CNS). The clinical relevance of this is unknown. We assessed CNS immune surveillance and metabolic activity involved in neuronal survival, in relation to fatigue and cognitive dysfunction in 25 long-term survivors after aHSCT. Patients with cognitive dysfunction exhibited increased proportions of activated T-cells and CD16 + NK-cells in the cerebrospinal fluid (CSF). Immune cell activation was paralleled with reduced levels of anti-inflammatory factors involved in T-cell suppression (transforming growth factor-β, programmed death ligand-1), NK-cell regulation (poliovirus receptor, nectin-2), and macrophage and microglia activation (CD200, chemokine [C-X3-C motif] ligand-1). Additionally, the CSF mRNA expression pattern was associated with neuroinflammation and oxidative stress. Furthermore, proteomic, and transcriptomic studies demonstrated decreased levels of neuroprotective factors, and an upregulation of apoptosis pathway genes. The kynurenine pathway of tryptophan metabolism was activated in the CNS of all aHSCT patients, resulting in accumulation of neurotoxic and pro-inflammatory metabolites. Cognitive decline and fatigue are overlooked but frequent complications of aHSCT. This study links post-transplant CNS inflammation and neurotoxicity to our previously reported hypoactivation in the prefrontal cortex during cognitive testing, suggesting novel treatment targets.
Keyphrases
- stem cell transplantation
- nk cells
- cerebrospinal fluid
- oxidative stress
- cognitive decline
- high dose
- transforming growth factor
- blood brain barrier
- cerebral ischemia
- prefrontal cortex
- end stage renal disease
- inflammatory response
- mild cognitive impairment
- anti inflammatory
- epithelial mesenchymal transition
- traumatic brain injury
- ejection fraction
- public health
- newly diagnosed
- ms ms
- chronic kidney disease
- adipose tissue
- dna damage
- neuropathic pain
- case control
- cell proliferation
- endoplasmic reticulum stress
- sleep quality
- prognostic factors
- risk factors
- single cell
- lps induced
- induced apoptosis
- peritoneal dialysis
- cell cycle arrest
- lipopolysaccharide induced
- young adults
- gene expression
- diabetic rats
- heat shock protein
- depressive symptoms
- spinal cord
- heat stress
- heat shock
- physical activity
- bioinformatics analysis