Sexual dimorphism in the cerebrospinal fluid total protein content

Castellazzi, Massimiliano; Pizzicotti, Stefano; Lombardo, Ilenia; Alfiero, Sarah; Morotti, Andrea; Pellegatti, Patrizia; Negri, G; Natali, Lara; Ferri, Caterina; Fainardi, Enrico; Bellini, Tiziana; Pugliatti, Maura

doi:10.1515/cclm-2020-0419

Cited by 9 publications

(19 citation statements)

References 24 publications

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“…Another study investigating a large cohort of 1,079,193 participants with unknown characteristics evaluated serum albumin and found sex differences depending on age [ 24 ]. In the current study, protein concentrations were also higher in male than in female patients, similar to previous studies [ 25 , 26 ]. Overall, the sex difference in Q Alb levels appears to be independent of neurological or psychiatric diagnoses, which therefore strongly suggests bias from some general factors associated with sex, which remain to be elucidated.…”

Section: Discussionsupporting

confidence: 92%

Sex difference in cerebrospinal fluid/blood albumin quotients in patients with schizophreniform and affective psychosis

Meixensberger

Bechter²,

Dersch

et al. 2020

Fluids Barriers CNS

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Background The importance of cerebrospinal fluid (CSF) diagnostics for psychiatry is growing. The CSF/blood albumin quotient (QAlb) is considered to be a measure of the blood–CSF barrier function. Recently, systematically higher QAlb in males than in females was described in neurological patients. The aim of this study was to investigate whether a sex difference could also be detected in a well-characterized psychiatric cohort. Methods The patient cohort comprised 989 patients, including 545 females and 444 males with schizophreniform and affective syndromes who underwent CSF diagnostics, including QAlb measurement. The basic CSF findings and antineuronal autoantibody data of this cohort have already been published. This re-analysis employed analysis of covariance with age correction for QAlb mean values and chi2-testing for the number of increased age-corrected QAlb levels to investigate sex differences in QAlb. Results The QAlb levels were elevated above reference levels by 18% across all patients, and a comparison between male and female patients revealed a statistically significant sex difference, with increased values in 26% of male patients and a corresponding rate of only 10% in female patients (chi2 = 42.625, p < 0.001). The mean QAlb values were also significantly higher in males (6.52 ± 3.69 × 10–3) than in females (5.23 ± 2.56 × 10–3; F = 52.837, p < 0.001). Discussion The main finding of this study was a significantly higher QAlb level in male compared to female patients with psychiatric disorders, complementing previously described sex differences in neurological patient cohorts. This result indicates bias from some general factors associated with sex and could be partly explained by sex differences in body height, which is associated with spine length and thus a longer distance for CSF flow within the subarachnoid space down the spine from the occipital area to the lumbar puncture site in males compared to females. Hormonal influences caused by different estrogen levels and other sex-specific factors could also play a relevant role. The significance of the study is limited by its retrospective design, absence of a healthy control group, and unavailability of exact measures of spine length.

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Section: Discussionsupporting

confidence: 92%

Sex difference in cerebrospinal fluid/blood albumin quotients in patients with schizophreniform and affective psychosis

Meixensberger

Bechter²,

Dersch

et al. 2020

Fluids Barriers CNS

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“…The higher CSF concentration of plasma-derived proteins in males compared to females is reflected in that males tend to have a higher CSF total protein content than females [18]. Different positivity thresholds have already been proposed for males and females with regards to the CSF total protein content [17] and their application effectively reduces the gap between the two sexes in laboratory reporting of high protein content [18,29]. Interestingly, in both sexes a marked pleocytosis is accompanied by a high CSF protein content while this association is not present for less severe pleocytosis.…”

Section: Discussionmentioning

confidence: 99%

“…CSF total protein content was measured in all samples as a part of the diagnostic work-up. As published before [ 18 ] analysis was performed on the 1st–4th mL of CSF after lumbar puncture within 2 h from sample withdrawal. CSF samples were analyzed at room temperature, immediately after centrifugation and with the Beckman Coulter AU640/AU640e automated chemistry analyzer (Beckman Instruments, Fullerton, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies on QAlb, have shown sex differences in B-CSF-B permeability in both hospital and general populations [ 14 ], in multiple sclerosis, and other inflammatory and noninflammatory neurological disorders [ 15 ] and in patients with schizophreniform and affective psychosis [ 16 ]. Such differences in the QAlb concentration produces a sexual dimorphism of the CSF protein concentrations wherein males have higher protein levels than females, independently of age [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…In recent years, the existence of sexual dimorphism at the level of CSF protein content has become increasingly evident, and in particular, these sex-related differences seem to concern all the concentrations of plasma-derived proteins [ 14 , 15 , 16 , 17 ]. It has emerged that QAlb is higher in males than females regardless of age as a consequence of a reduced CSF-flow rate (e.g., an increased transfer of protein from blood to CSF, reduced CSF elimination from CSF space into lymphatic organs or venous compartment) in the male sex.…”

Section: Introductionmentioning

confidence: 99%

The Sexual Dimorphism in Cerebrospinal Fluid Protein Content Does Not Affect Intrathecal IgG Synthesis in Multiple Sclerosis

Castellazzi

Ferri

Tecilla

et al. 2022

JPM

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(1) Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that mainly affects young adults and females more than males. The detection of intrathecal IgG synthesis (IIS) on cerebrospinal fluid (CSF) analysis supports the diagnosis of MS. A sexual dimorphism has recently been described in CSF protein content. (2) Methods: Clinical and laboratory data from 340 MS patients (F = 231, M = 99) and 89 people with clinically isolated syndrome (CIS) (F = 57, M = 32) were retrospectively analyzed to assess the presence of variables affected by sex and age. (3) Results: In MS, the albumin quotient (QAlb), reflecting the blood–CSF barrier (BCSFB) function, was higher in males (5.6 vs. 4.34) and correlated to age with a constant difference between sexes (F = 41.71). In CIS patients, QAlb increased with age only in males (r = 0.3567). Age was positively correlated to disease duration and severity in MS (r = 0.3502, r = 0.2986, respectively). No differences emerged for quantitative and qualitative IIS determinations. (4) Discussion: Although the main difference between males and females concerns the function of BCSFB assessed by QAlb, this sexual dimorphism does not affect the determination of the IIS evaluated both by quantitative and qualitative methods.

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Sexual dimorphism in the cerebrospinal fluid total protein content

Cited by 9 publications

References 24 publications

Sex difference in cerebrospinal fluid/blood albumin quotients in patients with schizophreniform and affective psychosis

Sex difference in cerebrospinal fluid/blood albumin quotients in patients with schizophreniform and affective psychosis

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

The Sexual Dimorphism in Cerebrospinal Fluid Protein Content Does Not Affect Intrathecal IgG Synthesis in Multiple Sclerosis

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