Cognitive impairments correlate with increased central nervous system immune activation after allogeneic haematopoietic stem cell transplantation
A) The kynurenine pathway of tryptophan metabolism was activated in all aHSCT patients. The levels of KYN and 3-HK, that readily cross the BBB, were increased in both plasma and CSF, while QUIN, that do not cross the BBB, was exclusively elevated in CSF, suggesting intrathecal production in microglia. QUIN and 3-HK have documented neurotoxic properties and may contribute to an underlying neurotoxic environment after aHSCT. B-D) Activated T-cells and CD16 + NK-cells were increased in the CSF of aHSCT patients with fatigue (C, D), coupled with decreased amounts of immune regulatory (green and blue dots) and neurotrophic (grey dots) proteins in the subgroup with cognitive dysfunction (D). In contrast, patients with normal cognition (B, C) had increased levels of reparative and anti-inflammatory factors, possibly counteracting the toxic environment highlighted by the increased apoptosis activity and signs of ongoing neuroinflammation observed in the mRNA sequencing analysis.