Cerebrospinal fluid cytokines in multiple system atrophy: A cross-sectional Catalan MSA registry study

被引：35

作者：

Compta, Yaroslau ^{[1
]}

Dias, Sara P. ^{[1
,2
]}

Giraldo, Darly M. ^{[1
]}

Perez-Soriano, Alexandra ^{[1
]}

Munoz, Esteban ^{[1
]}

Saura, Josep ^{[3
]}

Fernandez, Manel ^{[1
]}

Bravo, Paloma ^{[1
]}

Camara, Ana ^{[1
]}

Pulido-Salgado, Marta ^{[1
]}

Painous, Celia ^{[1
]}

Rios, Jose ^{[4
,5
]}

Jose Marti, Maria ^{[1
]}

Pagonabarraga, Javier ^{[1
,6
]}

Valldeoriola, Francesc ^{[1
]}

Hernandez-Vara, Jorge ^{[7
]}

Jauma Classen, Serge ^{[8
]}

Puente, Victor ^{[9
]}

Pont, Claustre ^{[10
]}

Caballol, Nuria ^{[11
]}

Tolosa, Eduardo ^{[1
]}

Bayes, Angels ^{[1
,12
]}

Campdelacreu, Jaume ^{[8
]}

de Fabregues, Oriol ^{[7
]}

Avila, Asuncion ^{[11
]}

Calopa, Matilde ^{[8
]}

Gaig, Caries ^{[1
]}

Fabregat, Neus ^{[13
]}

Pastor, Pau ^{[14
]}

Aguilar, Miquel ^{[14
]}

Pujol, Montserrat ^{[15
]}

Sanchez, Almudena ^{[1
]}

Planellas, Lluis ^{[1
]}

Ezquerra, Mario ^{[16
]}

Fernandez-Santiago, Ruben ^{[16
]}

Botta, Teresa ^{[17
]}

Tartaglia, Gian ^{[17
]}

机构：

[1] Univ Barcelona, Parkinsons Dis & Movement Disorders Unit, Inst Neurociencies, Hosp Clin IDIBAPS CIBERNED European Reference Net, Catalonia, Spain

[2] Ctr Hosp Lisboa Cent, Dept Neurol, Lisbon, Portugal

[3] Univ Barcelona, Biochem & Mol Biol Unit, Dept Biomed, Sch Med,Inst Neurociencies, Catalonia, Spain

[4] Univ Autonoma Barcelona, IDIBAPS, Med Stat Core Facil, Catalonia, Spain

[5] Univ Autonoma Barcelona, Fac Med, Biostat Unit, Catalonia, Spain

[6] Hosp Santa Creu & Sant Pau, Movement Disorders Unit, Barcelona, Catalonia, Spain

[7] Hosp Valle De Hebron, Movement Disorders Unit, Barcelona, Catalonia, Spain

[8] Hosp Bellvitge Princeps Espanya, Movement Disorders Unit, Barcelona, Catalonia, Spain

[9] Hosp Mar, Movement Disorders Unit, Barcelona, Catalonia, Spain

[10] Hosp Gen Granollers, Granollers, Catalonia, Spain

[11] Hosp St Joan Despi Moises Broggi Consorci Sanitar, Movement Disorders Unit, Lhospitalet De Llobregat, Catalonia, Spain

[12] Ctr Med Teknon, Movement Disorders Unit, Barcelona, Catalonia, Spain

[13] Hosp Plato, Barcelona, Catalonia, Spain

[14] Univ Hosp Mutua Terrassa, Neurol, Movement Disorders Unit, Terrassa, Catalonia, Spain

[15] Hosp Santa Maria Lleida, Lleida, Catalonia, Spain

[16] IDIBAPS, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

[17] Univ Pompeu Fabra, ICREA, Ctr Genom Regulat CRG, Gene Funct & Evolut Grp, Barcelona, Catalonia, Spain

来源：

PARKINSONISM & RELATED DISORDERS | 2019年 / 65卷

关键词：

Multiple system atrophy; Parkinson's disease; Cerebrospinal fluid; Cytokines; Inflammation; Biomarkers; NEUROFILAMENT LIGHT-CHAIN; ALPHA-SYNUCLEIN; FLT3; LIGAND; DIAGNOSIS; COENZYME-Q10; FRACTALKINE; DISEASE;

D O I：

10.1016/j.parkreldis.2019.05.040

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction: Neuroinflammation is a potential player in neurodegenerative conditions, particularly the aggressive ones, such as multiple system atrophy (MSA). Previous reports on cytokine levels in MSA using serum or cerebrospinal fluid (CSF) have been inconsistent, including small samples and a limited number of cytokines, often without comparison to Parkinson's disease (PD), a main MSA differential diagnosis. Methods: Cross-sectional study of CSF levels of 38 cytokines using a multiplex assay in 73 participants: 39 MSA patients (19 with parkinsonian type [MSAp], 20 with cerebellar type [MSAc]; 31 probable, 8 possible), 19 PD patients and 15 neurologically unimpaired controls. None of the participants was under non-steroidal anti-inflammatory drugs at the time of the lumbar puncture. Results: There were not significant differences in sex and age among participants. In global non-parametric comparisons FDR-corrected for multiple comparisons, CSF levels of 5 cytokines (FGF-2, IL-10, MCP-3, IL-12p40, MDC) differed among the three groups. In pair-wise FDR-corrected non-parametric comparisons 12 cytokines (FGF-2, eotaxin, fractalkine, IFN-alpha 2, IL-10, MCP-3, IL-12p40, MDC, IL-17, IL-7, MIP-1 beta, TNF-alpha) were significantly higher in MSA vs. non-MSA cases (PD + controls pooled together). Of these, MCP-3 and MDC were the most significant ones, also differed in MSA vs. PD, and were significant MSA-predictors in binary logistic regression models and ROC curves adjusted for age. CSF levels of fractalkine and MIP-1 alpha showed a strong and significant positive correlation with UMSARS-2 scores. Conclusion: Increased CSF levels of cytokines such as MCP-3, MDC, fractalkine and MIP-1 alpha deserve consideration as potential diagnostic or severity biomarkers of MSA.

引用

页码：3 / 12

页数：10

共 35 条

[1] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[2] Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFα, and INFγ concentrations are elevated in patients with atypical and idiopathic parkinsonism [J].

Brodacki, Bogdan ;

Staszewski, Jacek ;

Toczylowska, Beata ;

Kozlowska, Ewa ;

Drela, Nadzieja ;

Chalimoniuk, Malgorzata ;

Stepien, Adam .

NEUROSCIENCE LETTERS, 2008, 441 (02) :158-162

[3] Control of microglial neurotoxicity by the fractalkine receptor [J].

Cardona, Astrid E. ;

Pioro, Erik P. ;

Sasse, Margaret E. ;

Kostenko, Volodymyr ;

Cardona, Sandra M. ;

Dijkstra, Ineke M. ;

Huang, DeRen ;

Kidd, Grahame ;

Dombrowski, Stephen ;

Dutta, RanJan ;

Lee, Jar-Chi ;

Cook, Donald N. ;

Jung, Steffen ;

Lira, Sergio A. ;

Littman, Dan R. ;

Ransohoff, Richard M. .

NATURE NEUROSCIENCE, 2006, 9 (07) :917-924

[4] Cerebrospinal fluid levels of coenzyme Q10 are reduced in multiple system atrophy [J].

Compta, Yaroslau ;

Giraldo, Darly M. ;

Munoz, Esteban ;

Antonelli, Francesca ;

Fernandez, Manel ;

Bravo, Paloma ;

Soto, Marta ;

Camara, Ana ;

Torres, Ferran ;

Marti, Maria Jose .

PARKINSONISM & RELATED DISORDERS, 2018, 46 :16-23

[5] Cerebrospinal Tau, Phospho-Tau, and Beta-Amyloid and Neuropsychological Functions in Parkinson's Disease [J].

Compta, Yaroslau ;

Marti, Maria J. ;

Ibarretxe-Bilbao, Naroa ;

Junque, Carme ;

Valldeoriola, Francesc ;

Munoz, Esteban ;

Ezquerra, Mario ;

Rios, Jose ;

Tolosa, Eduardo .

MOVEMENT DISORDERS, 2009, 24 (15) :2203-2210

[6] CCL22 regulates experimental autoimmune encephalomyelitis by controlling inflammatory macrophage accumulation and effector function [J].

Dogan, Rukiye-Nazan E. ;

Long, Nancy ;

Forde, Eileen ;

Dennis, Kristen ;

Kohm, Adam P. ;

Miller, Stephen D. ;

Karpus, William J. .

JOURNAL OF LEUKOCYTE BIOLOGY, 2011, 89 (01) :93-104

[7] The β-chemokines CCL2 and CCL7 are two novel differentiation factors for midbrain dopaminergic precursors and neurons [J].

Edman, Linda C. ;

Mira, Helena ;

Arenas, Ernest .

EXPERIMENTAL CELL RESEARCH, 2008, 314 (10) :2123-2130

[8]

Fahn S., 1987, RECENT DEV PARKINSON, V2, P153, DOI DOI 10.2490/JJRMC.47.791

[9] Multiple-System Atrophy [J].

Fanciulli, Alessandra ;

Wenning, Gregor K. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (03) :249-263

[10] Second consensus statement on the diagnosis of multiple system atrophy [J].

Gilman, S. ;

Wenning, G. K. ;

Low, P. A. ;

Brooks, D. J. ;

Mathias, C. J. ;

Trojanowski, J. Q. ;

Wood, N. W. ;

Colosimo, C. ;

Duerr, A. ;

Fowler, C. J. ;

Kaufmann, H. ;

Klockgether, T. ;

Lees, A. ;

Poewe, W. ;

Quinn, N. ;

Revesz, T. ;

Robertson, D. ;

Sandroni, P. ;

Seppi, K. ;

Vidailhet, M. .

NEUROLOGY, 2008, 71 (09) :670-676

← 1 2 3 4 →