Sex-Related Differences in Cerebrospinal Fluid Plasma-Derived Proteins of Neurological Patients

Abstract

Background and aims: Cerebrospinal fluid (CSF) protein content presents a sexual dimorphism in humans. We investigated sex-related differences in CSF IgG levels and in the quantification of intrathecal IgG synthesis (IIS).

Methods: CSF, serum albumin and IgG were measured in 1519 neurological patients and both linear and hyperbolic formulas were used for the quantification of IIS. CSF-restricted oligoclonal IgG bands (OCBs) were used as "gold standard".

Results: The linear IgG Index showed a weak agreement with OCBs in males and females (k = 0.559, k = 0.587, respectively), while the hyperbolic Reiber's formulas had a moderate agreement with OCBs in females (k = 0.635) and a weak agreement in males (k = 0.565). Higher CSF albumin and IgG levels were found in men than in women in the whole population and in subjects without IIS after adjusting for age and for serum concentrations of albumin and IgG, respectively (Quade statistics, p < 0.000001). CSF and serum albumin and IgG levels positively correlated to age in both sexes. CSF total protein content did not correlate with CSF leukocyte numbers but was higher in patients with marked pleocytosis.

Conclusions: In neurological patients, men have higher levels of CSF serum-derived proteins, such as albumin and IgG.

Keywords: age; albumin quotient; blood-cerebrospinal fluid barrier; cerebrospinal fluid; humans; intrathecal IgG synthesis; sex.

Figure 1

Linear regression analysis of age and (a,b) cerebrospinal fluid (CSF) and serum (c,d) concentrations of albumin and IgG and their (e,f) CSF/serum quotients (QAlb and QIgG respectively) in female and male patients. Presence of an intrathecal IgG synthesis was tested through the “gold standard” of oligoclonal bands (OCBs), and only subjects negative for the presence of OCBs were analyzed. Outliers were determined with robust regression and outlier removal (ROUT) method and excluded from any single analysis. Correlations were computed with Spearman test and F-test was used in regression analysis to compare the fits of linear models. NA: not applicable; when the slopes differed so much, it was not possible to test whether the intercepts differed significantly.

Figure 2

(a) Cerebrospinal fluid (CSF) albumin and (b) IgG levels in patients negative for the presence of intrathecal IgG synthesis grouped by age. Light blue, men; pink, women. Mann–Whitney test was used for all comparisons. Bars represent medians and 95% confidence intervals.

Figure 3

Cerebrospinal fluid (CSF) total protein levels in patients grouped by pleocytosis severity; normal (no more than 5 cells/μL); mild (6–25 cells/μL); moderate (26–100 cells/μL); marked (more than 100 cells/μL). (a) Men; (b) women. Kruskall–Wallis with Dunn’s multiple comparisons test were used in both analyses. Bars represent medians and 95% confidence intervals.