Identification of novel candidate protein biomarkers for the post-polio syndrome - implications for diagnosis, neurodegeneration and neuroinflammation

被引:39
作者
Gonzalez, Henrik [2 ]
Ottervald, Jan [1 ,3 ]
Nilsson, Kerstin C. [4 ]
Sjogren, Niclas [5 ]
Miliotis, Tasso [6 ]
Von Bahr, Helena [6 ]
Khademi, Mohsen
Eriksson, Bodil [7 ]
Kjellstrom, Sven [8 ]
Vegvari, Akos [8 ]
Harris, Robert
Marko-Varga, Gyorgy [8 ]
Borg, Kristian [2 ]
Nilsson, Johan [9 ]
Laurell, Thomas [9 ]
Olsson, Tomas
Franzen, Bo [3 ]
机构
[1] Karolinska Hosp, CMM, Neuroimmunol Unit, Dept Clin Neurosci, S-17176 Stockholm, Sweden
[2] Karolinska Hosp, Danderyd Hosp, Dept Clin Sci, Div Rehabil Med, S-17176 Stockholm, Sweden
[3] AstraZeneca R&D Sodertalje, Mol Pharmacol, Sodertalje, Sweden
[4] AstraZeneca R&D Sodertalje, Local Discovery, Dis Biol, Sodertalje, Sweden
[5] AstraZeneca R&D Sodertalje, Biostat, Sodertalje, Sweden
[6] AstraZeneca R&D, Local Discovery, Biosci, Molndal, Sweden
[7] AstraZeneca R&D Sodertalje, BioPR&D, Sodertalje, Sweden
[8] AstraZeneca R&D, Local Discovery, Biol Sci, Lund, Sweden
[9] Lund Tech Univ, Lund, Sweden
基金
瑞典研究理事会; 英国医学研究理事会;
关键词
Post-polio syndrome; Pathophysiology; CSF; Proteomics; Biomarkers; Diagnosis; ALPHA-AMIDATING MONOOXYGENASE; CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; SPINAL-CORD; MULTIPLE-SCLEROSIS; INTRAVENOUS IMMUNOGLOBULIN; PRIOR POLIOMYELITIS; CYTOKINE PRODUCTION; HUMAN KALLIKREIN-6;
D O I
10.1016/j.jprot.2008.11.014
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, a condition known as post-polio syndrome (PPS). The condition affects 20-60% of previous polio patients, making it one of the most common causes of neurological deficits worldwide. The underlying pathogenesis is not fully understood and accurate diagnosis is not feasible. Herein we investigated whether it was possible to identify proteomic profile aberrations in the cerebrospinal fluid (CSF) of PPS patients. CSF from 15 patients with well-defined PPS were analyzed for protein expression profiles. The results were compared to data obtained from nine healthy controls and 34 patients with other non-inflammatory diseases which served as negative controls. In addition, 17 samples from persons with secondary progressive multiple sclerosis (SPMS) were added as relevant age-matched references for the PPS samples. The CSF of persons with PPS displayed a disease-specific and highly predictive (P=0.0017) differential expression of five distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase and kallikrein 6, respectively, in comparison with the control groups. An independent ELISA confirmed the increase of kallikrein 6. We suggest that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for PPS patients. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:670 / 681
页数:12
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