The associations between serum vascular endothelial growth factor, tumor necrosis factor and interleukin 4 with the markers of blood-brain barrier breakdown in patients with paraneoplastic neurological syndromes.

Abstract

The blood-brain barrier (BBB) disruption is a critical step in paraneoplastic neurological syndrome (PNS) development. Several cytokines have been implicated in BBB breakdown. However, the exact step-by-step mechanism in which PNS develops is unknown, and the relationship between a systemic neoplasm and BBB is multilevel. The aim of the present study was to examine serum markers of BBB breakdown (S100B protein, neuron-specific enolase, NSE) and concentrations of proinflammatory (TNF-alpha, VEGF) and anti-inflammatory/immunosuppressive cytokines (IL-4), and to establish their interrelationship in patients with PNS. We analyzed 84 patients seropositive for onconeural antibodies that originated from a cohort of 250 cases with suspected PNS. Onconeural antibodies were estimated with indirect immunofluorescence and confirmed with Western blotting. Serum S-100B was estimated using electrochemiluminescence immunoassay. NSE, VEGF, TNF-alpha and IL-4 were analyzed with ELISA. We found that S-100B protein and NSE serum concentrations were elevated in PNS patients without diagnosed malignancy, and S-100B additionally in patients with peripheral nervous system manifestation of PNS. Serum VEGF levels showed several abnormalities, including a decrease in anti-Hu positive patients and increase in PNS patients with typical manifestation and/or central nervous system involvement. Increase in TNF-alpha was observed in patients with undetermined antibodies. To conclude, the presence of paraneoplastic neurological syndrome in seropositive patients does not affect serum markers of BBB breakdown, with the exception of the group without clinically demonstrated malignancy and patients with peripheral manifestation of PNS. S-100B and NSE might increase during early phase of PNS. VEGF may be involved in typical PNS pathophysiology.

• Authors: Slawomir Michalak, Alicja Kalinowska-Lyszczarz, Joanna Rybacka-Mossakowska, Mikolaj Zaborowski, Wojciech Kozubski
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 126 Issue 2 Pg. 149-158 (Feb 2019) ISSN: 1435-1463 [Electronic] Austria
• PMID: 30374596 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Biomarkers, Tumor
• IL4 protein, human
• S100 Calcium Binding Protein beta Subunit
• S100B protein, human
• TNF protein, human
• Tumor Necrosis Factor-alpha
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Interleukin-4
• Phosphopyruvate Hydratase

Topics

• Adult
• Biomarkers (blood)
• Biomarkers, Tumor (blood, immunology)
• Blood-Brain Barrier (immunology, pathology)
• Cohort Studies
• Female
• Humans
• Interleukin-4 (blood)
• Male
• Middle Aged
• Paraneoplastic Syndromes, Nervous System (blood, immunology)
• Phosphopyruvate Hydratase (blood)
• S100 Calcium Binding Protein beta Subunit (blood)
• Tumor Necrosis Factor-alpha (blood)
• Vascular Endothelial Growth Factor A (blood)