Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis:
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Ulm
2016
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| 245 | 1 | 0 | |a Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis |c submitted by André Michael Huss |
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| adam_text | ULM
UNIVERSITY UNIVERSITAET I
UULM
ULM UNIVERSITY HOSPITAL | DEPARTMENT OF NEUROLOGY
PROF. DR. MARKUS OTTO
PROSPECTIVE MULTI-CENTER VALIDATION AND
PROTEOMIC DISCOVERY OF CANDIDATE CSF PROTEIN
BIOMARKERS IN MULTIPLE SCLEROSIS
DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE DEGREE OF *DOCTOR RERUM NATURALIUM* (DR. RER. NAT.) OF THE
INTERNATIONAL GRADUATE SCHOOL IN MOLECULAR MEDICINE ULM (IGRADU)
SUBMITTED BY
ANDRE MICHAEL HUSS
BORN IN EHINGEN (DONAU)
ULM 2016
TABLE OF CONTENTS
DATA
PAGE.................................................................................................................................I
THESIS ADVISORY
COMMITTEE..................................................................................................II
INFORMATION ABOUT
PUBLICATIONS...........................................................................................ILL
ABBREVIATIONS........................................................................................................................
IV
TABLE OF
CONTENTS.................................................................................................................VI
1.
INTRODUCTION...................................................................................................................1
-
1.1 MULTIPLE SCLEROSIS
...............................................................................................
-1 -
1.1.1 DISEASE PATHOLOGY
....................................................................................
- 2 -
1.1.2 DIAGNOSIS OF MULTIPLE
SCLEROSIS................................................................-
2 -
1.2 CEREBROSPINAL
FLUID...........................................................................................-
3 -
1.3 BIOMARKERS IN MULTIPLE SCLEROSIS
....................................................................
- 3 -
1.3.1 OLIGOCLONAL IGG
BANDS...............................................................................-
4 -
1.3.2 THE MRZ
REACTION.......................................................................................-
5 -
1.3.3 C XC
L13.......................................................................................................-
6 -
1.3.4 GLIAL FIBRILLARY ACIDIC PROTEIN (G FAP)
.........................................................
- 6 -
1.3.5
NEUROFILAMENTS............................................................................................
- 6 -
1.4
IMMUNOASSAYS.................................................................................................-
7 -
1.5
PROTEOMICS.........................................................................................................-
8 -
1.5.1 ISOBARIC TAGS FOR RELATIVE AND ABSOLUTE QUANTITATION (ITRAQ)
...........
- 9 -
1.6 AIMS OF THE
STUDY.............................................................................................-1
0 -
2. MATERIAL AND
METHODS..........................................................................................
-1 2 -
2.1 PATIENTS AND
SAMPLES....................................................................................
-14-
2.2 DETERMINATION OF ALBUMIN AND IGG CONCENTRATIONS AND CSF/SERUM
QUOTIENTS
...........................................................................................................................
-15-
2.3 ROUTINE OCB ANALYSIS BY ISOELECTRIC FOCUSING ON POLYACRYLAMIDE GELS
WITH
SUBSEQUENT
IMMUNOBLOTTING...........................................................................
-1 5 -
2.4 DETERMINATION OF THE M
RZR...........................................................................-16-
2.4.1 MEASUREMENTS OF ANTIBODY CONCENTRATIONS AGAINST MEASLES, RUBELLA,
VARICELLA ZOSTER AND HERPES SIMPLEX IN CSF AND SERUM
.................
-1 6 -
2.4.2 CALCULATIONS OF ANTIBODY SPECIFICITY INDICES (A SIS)
..........................
-1 6 -
2.5 DETERMINATION OF CXCL13 LEVELS IN C S F
....................................................-17-
2.6 DETERMINATION OF GFAP LEVELS IN THE C S F
..................................................-17-
2.7 DETERMINATION OF NFL LEVELS IN THE C S F
....................................................
-1 8 -
2.8 ITRAQ
MEASUREMENTS..................................................................................
-1 8 -
2.8.1 SAMPLE
PREPARATION...............................................................................-1
8 -
2.8.2 LABELING WITH ITRAQ
REAGENT...............................................................-1
9 -
2.8.3 SCX
FRACTIONATION...................................................................................
-19-
2.8.4 LC-MASS SPEC
ANALYSIS.........................................................................-
20 -
2.8.5 DATA ANALYSIS AND
BIOINFORMATICS........................................................-
21 -
2.9 DETERMINATION OF GLIOMEDIN
LEVELS..............................................................- 22
-
2.10 DETERMINATION OF TENASCIN C
LEVELS.............................................................- 2 2
-
2.11 DETERMINATION OF AUTOANTIBODIES AGAINST GLIOMEDIN
................................
- 23 -
2.12
STATISTICS..........................................................................................................
-24-
3.
RESULTS....................................................................................................................
- 26 -
3.1 MULTICENTER VALIDATION AND CHARACTERIZATION OF
BIOMARKERS.....................- 26 -
3.1.1 COLLECTION OF MULTICENTER
SAMPLES....................................................... - 26 -
3.1.2 VALIDATION OF THE M
RZR..........................................................................
-26-
3.1.3 CHARACTERIZATION OF CXCL13
............................................................... - 33 -
3.1.4 CHARACTERIZATION OF G
FAP....................................................................-
37 -
3.1.5 CHARACTERIZATION OF
NFL........................................................................
- 41 -
3.2 IDENTIFICATION OF NEW CANDIDATE
BIOMARKERS.............................................-4 5 -
3.2.1 COHORTS USED FOR IDENTIFICATION OF BIOMARKER CANDIDATES
................
-4 5 -
3.2.2 CANDIDATE BIOMARKER IDENTIFICATION USING IT R A Q
............................
- 46 -
3.2.3 VALIDATION OF TENASCIN C AS A BIOMARKER FOR M S
...............................- 52 -
3.2.4 VALIDATION OF GLIOMEDIN AS A BIOMARKER FOR M S
................................- 54 -
3.2.5 DETECTION OF GLIOMEDIN AUTOANTIBODIES
........................
......................
- 54 -
4.
DISCUSSION.............................................................................................................-
57 -
5.
SUMMARY................................................................................................................
-65-
6.
REFERENCES............................................................................................................-
67 -
7.
BIBLIOGRAPHY..........................................................................................................
- 80 -
8.
ACKNOWLEDGEMENTS..............................................................................................
- 82 -
9. STATUTORY
DECLARATION............................................................................................-
83 -
|
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| author | Huss, André Michael |
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| dewey-ones | 610 - Medicine and health |
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| discipline | Medizin |
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| spelling | Huss, André Michael Verfasser (DE-588)1132273633 aut Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis submitted by André Michael Huss Ulm 2016 VII, 83 Blätter Illustrationen 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation International Graduate School in Molecular Medicine Ulm 2017 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf http://d-nb.info/1132590329/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029807438&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Huss, André Michael Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis |
| subject_GND | (DE-588)4113937-9 |
| title | Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis |
| title_auth | Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis |
| title_exact_search | Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis |
| title_full | Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis submitted by André Michael Huss |
| title_fullStr | Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis submitted by André Michael Huss |
| title_full_unstemmed | Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis submitted by André Michael Huss |
| title_short | Prospective multi-center validation and proteomic discovery of candidate CSF protein biomarkers in multiple sclerosis |
| title_sort | prospective multi center validation and proteomic discovery of candidate csf protein biomarkers in multiple sclerosis |
| topic_facet | Hochschulschrift |
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