Location matters: highly divergent protein levels in samples from diferent CNS compartments in a clinical trial of rituximab for progressive MS

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Bergman, JoakimUppsala universitet,Umeå universitet,Neurovetenskaper,Umeå Univ, Dept Clin Sci, S-90185 Umeå, Sweden.,Landtblom: Neurovetenskap (författare)

Location matters : highly divergent protein levels in samples from diferent CNS compartments in a clinical trial of rituximab for progressive MS

Artikel/kapitelEngelska2020

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2020-07-29
BioMed Central,2020
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:umu-169319
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-169319URI
https://doi.org/10.1186/s12987-020-00205-4DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:144329524URI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-420810URI

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Språk:engelska
Sammanfattning på:engelska

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Originally included in thesis in manuscript form, with title: "Location matters: highly divergent protein levels in samples from different CNS compartments"
Background: The relationship between proteins in different CNS extracellular compartments is unknown. In this study the levels of selected proteins in three compartments in people with progressive multiple sclerosis (PMS) were compared.Methods: During an open label, phase 1b study on intraventricular administration of rituximab for PMS, samples were collected from the interstitial space (ISS) of the brain through microdialysis. Samples were also obtained from ventricular and lumbar cerebrospinal fluid (CSF). These samples were analyzed with a multiplexed proximity extension assay, measuring the levels of 180 proteins split equally between two panels, detecting proteins associated with immunology and neurology, respectively.Results: Considerable differences in concentrations were observed between the three analyzed compartments. Compared to ventricular CSF, ISS fluid contained statistically significant higher levels of 25 proteins (84% immunology panel and 16% neurology panel). Ventricular CSF contained significantly higher levels of 54 proteins (31% immunology panel and 69% neurology panel) compared to ISS fluid, and 17 proteins (76% immunology panel and 24% neurology panel) compared to lumbar CSF. Lumbar CSF showed significantly higher levels of 115 proteins (32% immunology panel and 68% neurology panel) compared to ventricular CSF. The three compartments displayed poor correlation with a median Spearman’s rho of -0.1 (IQR 0.4) between ISS and ventricular CSF and 0.3 (IQR 0.4) between ventricular and lumbar CSF.Conclusion: A substantial heterogeneity in the protein levels of samples obtained from different CNS compartments was seen. Therefore, data obtained from analysis of lumbar CSF should be interpreted with caution when making conclusions about pathophysiological processes in brain tissue.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
Cerebrospinal fuid
Microdialysis
Ventricular CSF
Lumbar CSF
Interstitial fuid
CSF compartments
CSF proteins
Progressive MS

Biuppslag (personer, institutioner, konferenser, titlar ...)

Svenningsson, AndersKarolinska Institutet,Umeå universitet,Neurovetenskaper,Department of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden,Umeå Univ, Dept Clin Sci, S-90185 Umeå, Sweden.;Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.(Swepub:umu)ansv0041 (författare)
Liv, Per,1979-Umeå universitet,Avdelningen för medicin,Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden.(Swepub:umu)perliv00 (författare)
Bergenheim, A. TommyUmeå universitet,Neurovetenskaper,Umeå Univ, Dept Clin Sci, S-90185 Umeå, Sweden.(Swepub:umu)tobe0004 (författare)
Burman, Joachim (författare)
Umeå universitetNeurovetenskaper (creator_code:org_t)

Sammanhörande titlar

Ingår i:Fluids and Barriers of the CNS: BioMed Central:12045-8118

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Fluids and Barriers of the CNS (Sök värdpublikationen i LIBRIS)

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Av författaren/redakt...: Bergman, Joakim; Svenningsson, An ...; Liv, Per, 1979-; Bergenheim, A. T ...; Burman, Joachim

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