A chronic fatigue syndrome - related proteome in human cerebrospinal fluid

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http://www.biomedcentral.com/1471-2377/5/22/abstract

Research article

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A chronic fatigue syndrome - related proteome in human cerebrospinal fluid

N. Baraniuk baraniuj@...

Begona Casado bc48@...

Hilda Maibach hildamaibach@...

J. Clauw dclauw@...

K. Pannell lpannell@...

Sonja Hess S Sonja_Hess@...

BMC Neurology 2005, 5:22 doi:10.1186/1471-2377-5-22

Published 1 December 2005

Abstract (provisional)

Background

Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and

fibromyalgia are overlapping symptom complexes without objective markers

or known pathophysiology. Neurological dysfunction is common. We

assessed cerebrospinal fluid to find proteins that were differentially

expressed in this CFS-spectrum of illnesses compared to control subjects.

Methods

Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control

subjects (50 mul/subject) were pooled into one sample per group (cohort

1). Cohort 2 of 12 control and 9 CFS subjects had their fluids (200

mul/subject) assessed individually. After trypsin digestion, peptides

were analyzed by capillary chromatography, quadrupole-time-of-flight

mass spectrometry, peptide sequencing, bioinformatic protein

identification, and statistical analysis.

Results

Pooled CFS and PGI samples shared 20 proteins that were not detectable

in the pooled control sample (cohort 1 CFS-related proteome).

Multilogistic regression analysis (GLM) of cohort 2 detected 10 proteins

that were shared by CFS individuals and the cohort 1 CFS-related

proteome, but were not detected in control samples. Detection of >1 of a

select set of 5 CFS-related proteins predicted CFS status with 80%

concordance (logistic model). The proteins were alpha-1-macroglobulin,

amyloid precursor-like protein 1, keratin 16, orosomucoid 2 and pigment

epithelium-derived factor. Overall, 62 of 115 proteins were newly described.

Conclusion

This pilot study detected an identical set of central nervous system,

innate immune and amyloidogenic proteins in cerebrospinal fluids from

two independent cohorts of subjects with overlapping CFS, PGI and

fibromyalgia. Although syndrome names and definitions were different,

the proteome and presumed pathological mechanism(s) may be shared.

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