A Chronic Fatigue Syndrome - related proteome in human cerebrospinal fluid.
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 >or=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.


CONCLUSIONS
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.
Baraniuk
James N
JN
Georgetown University Proteomics Laboratory, Division of Rheumatology, Immunology & Allergy, Room B-105, Lower Level Kober-Cogan Building, Georgetown University, Washington, DC 20007-2197, USA. baraniuj@georgetown.edu
Casado
Begona
B
Maibach
Hilda
H
Clauw
Daniel J
DJ
Pannell
Lewis K
LK
Hess S
Sonja
S
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D002556:Cerebrospinal Fluid Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D015331:Cohort Studies; D003710:Demography; D003863:Depression / Q000150:complications; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005163:Factor Analysis, Statistical; D015673:Fatigue Syndrome, Chronic / Q000134:cerebrospinal fluid* / Q000150:complications; D005356:Fibromyalgia / Q000134:cerebrospinal fluid / Q000150:complications; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications; D007526:Isoelectric Point; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D008954:Models, Biological; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D018923:Persian Gulf Syndrome / Q000134:cerebrospinal fluid / Q000150:complications; D010555:Personality Inventory; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods; D012720:Severity of Illness Index; D013223:Statistics as Topic
D002556:Cerebrospinal Fluid Proteins