Differential expression of complement proteins in cerebrospinal fluid from active multiple sclerosis patients

Li, Yun; Qin, Zhaoyu; Yang, Ming-Chong; Qin, Yanjiang; Lin, Chengzhao; Liu, Shilian

doi:10.1002/jcb.23113

Cited by 22 publications

(37 citation statements)

References 39 publications

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“…In summary, our data do not support the finding of lower levels of fH in active MS reported by Li et al [2011]. The reasons for this are unclear but may relate to small sample numbers or the pooled analysis methodology employed by Li et al In contrast, we have demonstrated higher levels of both CSF and serum fH in progressive disease and an influx of systemic fH at times of breakdown of the blood-CSF barrier.…”

contrasting

confidence: 99%

“…T he recent paper by Li et al [2011] published in this journal demonstrated altered expression of three complement proteins, including factor H (fH), in pooled cerebrospinal fluid (CSF) from 12 patients with active multiple sclerosis (MS) compared to 12 patients with other unspecified neurological diseases. This timely data adds to the growing evidence implicating complement in active disease.…”

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confidence: 99%

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Complement regulator factor H in multiple sclerosis

et al. 2011

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A recent proteomic study published in this journal demonstrated lower cerebrospinal fluid (CSF) expression of factor H (fH), an important complement regulator, along with two other complement proteins, in active multiple sclerosis (MS) patients. We have previously demonstrated raised serum fH levels in MS and here, an extended analysis, quantifying fH in CSF, demonstrates no change in fH levels in active disease, but significantly raised levels in progressive disease. These findings support our previous work showing raised serum fH in patients with progressive MS, and our results predict that CSF fH levels will be raised rather than reduced in active disease.

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Complement regulator factor H in multiple sclerosis

et al. 2011

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“…Another study has also found an increased expression of C3, as well as C4b (an active peptide generated by the cleavage of C4) in the CSF of patients with acute RRMS when compared to healthy controls [23]. Moreover, plasma C4a (a fragment resulting from cleavage of C4) levels were significantly elevated in patients with active RRMS when compared to both controls and patients with stable RRMS [19].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, quantifying factor H levels in CSF indicated no change during active disease but significantly raised levels in progressive MS [29]. However, Li et al have found a decrease in the expression of factor H in the CSF of RRMS patients with active disease when compared to controls [23]. …”

Section: Introductionmentioning

confidence: 99%

The complement system as a biomarker of disease activity and response to treatment in multiple sclerosis

et al. 2017

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Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The complement system has an established role in the pathogenesis of MS, and evidence suggests that its components can be used as biomarkers of disease-state activity and response to treatment in MS. Plasma C4a levels have been found to be significantly elevated in patients with active relapsing-remitting MS (RRMS), as compared to both controls and patients with stable RRMS. C3 levels are also significantly elevated in the cerebrospinal fluid (CSF) of patients with RRMS, and C3 levels are correlated with clinical disability. Furthermore, increased levels of factor H can predict the transition from relapsing to progressive disease, since factor H levels have been found to increase progressively with disease progression over a 2-year period in patients transitioning from RRMS to secondary progressive (SP) MS. In addition, elevations in C3 are seen in primary progressive (PP) MS. Complement components can also differentiate RRMS from neuromyelitis optica. Response gene to complement (RGC)-32, a novel molecule induced by complement activation, is a possible biomarker of relapse and response to glatiramer acetate (GA) therapy, since RGC-32 mRNA expression is significantly decreased during relapse and increased in responders to GA treatment. The predictive accuracy of RGC-32 as a potential biomarker (by ROC analysis) is 90% for detecting relapses and 85% for detecting a response to GA treatment. Thus, complement components can serve as biomarkers of disease activity to differentiate MS subtypes and to measure response to therapy.

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“…There is currently a need for MS biomarkers that can help with earlier diagnosis, prediction, and evaluation of disease progression, and for monitoring treatment response . Several studies have focused on finding such biomarkers by comparing the proteins expressed in CSF between MS patients and controls . For most of the discovery studies, however, a low number of samples are included, or relatively few proteins are identified and quantified .…”

Section: Introductionmentioning

confidence: 99%

Label‐free analysis of human cerebrospinal fluid addressing various normalization strategies and revealing protein groups affected by multiple sclerosis

et al. 2016

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The aims of the study were to: (i) identify differentially regulated proteins in cerebrospinal fluid (CSF) between multiple sclerosis (MS) patients and non-MS controls; (ii) examine the effect of matching the CSF samples on either total protein amount or volume, and compare four protein normalization strategies for CSF protein quantification. CSF from MS patients (n = 37) and controls (n = 64), consisting of other noninflammatory neurological diseases (n = 50) and non neurological spinal anesthetic subjects (n = 14), were analyzed using label-free proteomics, quantifying almost 800 proteins. In total, 122 proteins were significantly regulated (p < 0.05), where 77 proteins had p-value <0.01 or AUC value >0.75. Hierarchical clustering indicated that there were two main groups of MS patients, those with increased levels of inflammatory response proteins and decreased levels of proteins involved in neuronal tissue development (n = 30), and those with normal protein levels for both of these protein groups (n = 7). The main subgroup of controls clustering with the MS patients showing increased inflammation and decreased neuronal tissue development were patients suffering from chronic fatigue. Our data indicate that the preferable way to quantify proteins in CSF is to first match the samples on total protein amount and then normalize the data based on the median intensities, preferably from the CNS-enriched proteins.

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Differential expression of complement proteins in cerebrospinal fluid from active multiple sclerosis patients

Cited by 22 publications

References 39 publications

Complement regulator factor H in multiple sclerosis

Complement regulator factor H in multiple sclerosis

The complement system as a biomarker of disease activity and response to treatment in multiple sclerosis

Label‐free analysis of human cerebrospinal fluid addressing various normalization strategies and revealing protein groups affected by multiple sclerosis

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