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. 2024 Jan 9:14:1330484.
doi: 10.3389/fneur.2023.1330484. eCollection 2023.

Comparative analysis of albumin quotient and total CSF protein in immune-mediated neuropathies: a multicenter study on diagnostic implications

Tabea Seeliger  1 , Stefan Gingele  1 , Yunus Emre Güzeloglu  1 , Lena Heitmann  1 , Benjamin Lüling  2 , Felix Kohle  3 , Hannah Preßler  4   5 , Frauke Stascheit  4   5 , Jeremias Motte  2 , Anna Lena Fisse  2 , Thomas Grüter  2 , Kalliopi Pitarokoili  2 , Thomas Skripuletz  1
Affiliations

Comparative analysis of albumin quotient and total CSF protein in immune-mediated neuropathies: a multicenter study on diagnostic implications

Tabea Seeliger et al. Front Neurol. .

Abstract

Introduction: Blood-cerebrospinal fluid (CSF) barrier dysfunction is pivotal for diagnosing immune-mediated neuropathies, especially in spinal nerve root inflammation. Typically, either total CSF protein or the CSF to serum albumin ratio (QAlb) is measured. Total CSF protein measurements have limitations, notably its fixed reference value regardless of age, in contrast to the age-dependent reference for QAlb. Our goal was to evaluate both markers in patients with immune-mediated neuropathies.

Methods: In our multicenter research, we collected retrospective CSF data from patients suffering from immune-mediated neuropathies across four German research centers. These parameters were analyzed in relation to their clinical characteristics.

Results: Out of 419 samples, 36 (8.6%) displayed a notable variation between total CSF protein and QAlb values. A detailed analysis revealed that patients displaying elevated QAlb but normal total CSF protein levels were significantly younger at disease onset (p = 0.01), at the time of diagnosis (p = 0.005), and when undergoing lumbar puncture (p = 0.001) compared to patients with elevated CSF protein and normal QAlb levels. These effects were especially evident for the subgroup of samples derived by female patients.

Discussion: Our work confirms the crucial role of QAlb in diagnosing immune-mediated neuropathies and particularly its efficacy as a marker for evaluating the blood-CSF barrier in patients with an earlier disease onset. Considering the significance of the albumin quotient, its assessment is especially advisable in younger patients of female sex to avoid missing a potential barrier dysfunction that might be falsely negative when using total protein.

Keywords: CSF; QAlb; barrier-dysfunction; blood-cerebrospinal fluid-barrier; immune-mediated neuropathies.

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Conflict of interest statement

TSe reports support for attending meetings by Abbvie. SG reports research support from Alnylam Pharmaceuticals, CSL Behring, Else Kröner Fresenius Foundation, Deutsche Forschungsgemeinschaft and Hannover Biomedical Research School (HBRS) and consulting and/or speaker honoraria from Alexion, Alnylam Pharmaceuticals, AstraZeneca, GSK, Pfizer and Merck all outside the submitted work. JM reports research grants by Biogen and Deutsche Forschungsgemeinschaft, stock/stock options at Biontech and CureVac, as well as support for attending meetings and/or travel by Biogen, Novartis and Alnylam. JM also received honoraria or lectures/ manuscripts by Biogen. KP reports research grants by Biogen idec, Novartis, Celgene, CSL Behring, Grifols, honoraria for lectures from CSL Behring, Grifols, participation on an Advisory Board 2021 by Celgene and non-paid consultant activity for patients organizations POTS and Dysautonomie e.V. TSk reports honoraria for lectures and travel expenses for attending meetings from Alexion, Alnylam Pharmaceuticals, argenx, Bayer Vital, Biogen, Celgene, Centogene, CSL Behring, Euroimmun, Janssen-Cilag, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens, Swedish Orphan Biovitrum, Teva, Viatris. His research is supported by the German Ministry for Education and Research (BMBF), Bristol-Myers Squibb Foundation for Immuno-Oncology, Claudia von Schilling Foundation for Breast Cancer Research, Else Kröner Fresenius Foundation, Hannover Biomedical Research School (HBRS), Alnylam Pharmaceuticals, CSL Behring, Novartis, Sanofi Genzyme, VHV Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Currently prompted diagnoses for included samples. N, number; CIDP, chronic inflammatory demyelinating polyneuropathy; MMN, multifocal motor neuropathy; GBS, Guillain-Barré syndrome.
Figure 2
Figure 2
Comparison of the blood-CSF dysfunction-markers QAlb and total CSF protein. Blue/ dotted lines—elevated QAlb calculated by age-dependent Reiber-formula (21); yellow—elevated total CSF protein >500 mg/L; green overlapping background/ black frame—both elevated QAlb and elevated total CSF protein as previously defined. Percentage values refer to the total sample size of 419 samples. N, number; CSF, cerebrospinal fluid; QAlb, ratio of CSF and serum albumin concentrations.
Figure 3
Figure 3
Correlation analysis of QAlb and total CSF protein values (Spearman’s rho coefficient = 0.96, p < 0.0001). CSF, cerebrospinal fluid; QAlb, ratio of CSF and serum albumin concentrations.
See this image and copyright information in PMC

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