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Erschienen in: Journal of Neurology 9/2023

06.06.2023 | Original Communication

Association between peripheral adaptive immune markers and disease progression in Parkinson's disease

verfasst von: Yi Xiao, Qianqian Wei, Ruwei Ou, Tianmi Yang, Qirui Jiang, Yanbing Hou, Lingyu Zhang, Kuncheng Liu, Shichan Wang, Junyu Lin, Bi Zhao, Wei Song, Xueping Chen, Ying Wu, Chunyu Li, Huifang Shang

Erschienen in: Journal of Neurology | Ausgabe 9/2023

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Abstract

Background

The pathogenesis of PD has not been fully elucidated, but recent studies have shown that the adaptive immune system may play a role in the pathology of PD. However, there is a lack of longitudinal studies exploring the relationship between peripheral adaptive immune indicators and the rate of disease progression in PD.

Methods

We included early PD patients with disease duration < 3 years and assessed the severity of clinical symptoms and peripheral adaptive immune system indicators (CD3+, CD4+, CD8+ T lymphocyte subsets, CD4+:CD8+ ratio, IgG, IgM, IgA, C3, C4) at baseline. Clinical symptoms were followed up every year. We used the Unified Parkinson's Disease Rating Scale (UPDRS) to assess the disease severity and the Montreal Cognitive Assessment (MoCA) to assess global cognitive function.

Result

A total of 152 PD patients were eventually included. The linear mixed model showed no significant association between baseline peripheral blood adaptive immune indicators and baseline MoCA scores or UPDRS part III scores. A higher baseline CD3+ lymphocyte percentage was associated with a slower rate of decline in MoCA scores. Baseline immune indicators were not associated with the rate of change of the UPDRS part III scores.

Conclusion

The subset of peripheral T lymphocytes was related to the rate of cognitive decline in early PD patients, suggesting that the peripheral adaptive immune system may be involved in the process of cognitive decline in early PD.
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Literatur
1.
Zurück zum Zitat Grimes D, Fitzpatrick M, Gordon J, Miyasaki J, Fon EA, Schlossmacher M, Suchowersky O, Rajput A, Lafontaine AL, Mestre T, Appel-Cresswell S, Kalia SK, Schoffer K, Zurowski M, Postuma RB, Udow S, Fox S, Barbeau P, Hutton B (2019) Canadian guideline for Parkinson disease. CMAJ 191:E989–E1004CrossRefPubMedPubMedCentral Grimes D, Fitzpatrick M, Gordon J, Miyasaki J, Fon EA, Schlossmacher M, Suchowersky O, Rajput A, Lafontaine AL, Mestre T, Appel-Cresswell S, Kalia SK, Schoffer K, Zurowski M, Postuma RB, Udow S, Fox S, Barbeau P, Hutton B (2019) Canadian guideline for Parkinson disease. CMAJ 191:E989–E1004CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Li CY, Yang TM, Ou RW, Wei QQ, Shang HF (2021) Genome-wide genetic links between amyotrophic lateral sclerosis and autoimmune diseases. BMC Med 19:27CrossRefPubMedPubMedCentral Li CY, Yang TM, Ou RW, Wei QQ, Shang HF (2021) Genome-wide genetic links between amyotrophic lateral sclerosis and autoimmune diseases. BMC Med 19:27CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Kustrimovic N, Marino F, Cosentino M (2019) Peripheral immunity, immunoaging and neuroinflammation in Parkinson’s disease. Curr Med Chem 26:3719–3753CrossRefPubMed Kustrimovic N, Marino F, Cosentino M (2019) Peripheral immunity, immunoaging and neuroinflammation in Parkinson’s disease. Curr Med Chem 26:3719–3753CrossRefPubMed
4.
Zurück zum Zitat Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM (2005) A possible role for humoral immunity in the pathogenesis of Parkinson’s disease. Brain J Neurol 128:2665–2674CrossRef Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM (2005) A possible role for humoral immunity in the pathogenesis of Parkinson’s disease. Brain J Neurol 128:2665–2674CrossRef
5.
Zurück zum Zitat Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S (2009) Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 119:182–192PubMed Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S (2009) Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 119:182–192PubMed
6.
Zurück zum Zitat Galiano-Landeira J, Torra A, Vila M, Bové J (2020) CD8 T cell nigral infiltration precedes synucleinopathy in early stages of Parkinson’s disease. Brain J Neurol 143:3717–3733CrossRef Galiano-Landeira J, Torra A, Vila M, Bové J (2020) CD8 T cell nigral infiltration precedes synucleinopathy in early stages of Parkinson’s disease. Brain J Neurol 143:3717–3733CrossRef
7.
Zurück zum Zitat Kouli A, Camacho M, Allinson K, Williams-Gray CH (2020) Neuroinflammation and protein pathology in Parkinson’s disease dementia. Acta Neuropathol Commun 8:211CrossRefPubMedPubMedCentral Kouli A, Camacho M, Allinson K, Williams-Gray CH (2020) Neuroinflammation and protein pathology in Parkinson’s disease dementia. Acta Neuropathol Commun 8:211CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Yamada T, Akiyama H, McGeer PL (1990) Complement-activated oligodendroglia: a new pathogenic entity identified by immunostaining with antibodies to human complement proteins C3d and C4d. Neurosci Lett 112:161–166CrossRefPubMed Yamada T, Akiyama H, McGeer PL (1990) Complement-activated oligodendroglia: a new pathogenic entity identified by immunostaining with antibodies to human complement proteins C3d and C4d. Neurosci Lett 112:161–166CrossRefPubMed
9.
Zurück zum Zitat Yamada T, McGeer PL, McGeer EG (1992) Lewy bodies in Parkinson’s disease are recognized by antibodies to complement proteins. Acta Neuropathol 84:100–104CrossRefPubMed Yamada T, McGeer PL, McGeer EG (1992) Lewy bodies in Parkinson’s disease are recognized by antibodies to complement proteins. Acta Neuropathol 84:100–104CrossRefPubMed
10.
Zurück zum Zitat Veselý B, Dufek M, Thon V, Brozman M, Királová S, Halászová T, Koriťáková E, Rektor I (2018) Interleukin 6 and complement serum level study in Parkinson’s disease. J Neural Transm (Vienna, Austria: 1996) 125:875–881CrossRef Veselý B, Dufek M, Thon V, Brozman M, Királová S, Halászová T, Koriťáková E, Rektor I (2018) Interleukin 6 and complement serum level study in Parkinson’s disease. J Neural Transm (Vienna, Austria: 1996) 125:875–881CrossRef
11.
Zurück zum Zitat Sun C, Yu W, Zhao Z, Song C, Liu Y, Jia G, Wang X, Liu Y (2019) Peripheral humoral immune response is associated with the non-motor symptoms of Parkinson’s disease. Front Neurosci 13:1057CrossRefPubMedPubMedCentral Sun C, Yu W, Zhao Z, Song C, Liu Y, Jia G, Wang X, Liu Y (2019) Peripheral humoral immune response is associated with the non-motor symptoms of Parkinson’s disease. Front Neurosci 13:1057CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Jiang S, Gao H, Luo Q, Wang P, Yang X (2017) The correlation of lymphocyte subsets, natural killer cell, and Parkinson’s disease: a meta-analysis. Neurol Sci 38:1373–1380CrossRefPubMed Jiang S, Gao H, Luo Q, Wang P, Yang X (2017) The correlation of lymphocyte subsets, natural killer cell, and Parkinson’s disease: a meta-analysis. Neurol Sci 38:1373–1380CrossRefPubMed
13.
Zurück zum Zitat Hu ZX, Song WN, Lu XD, Zhou ML, Shao JH (2018) Peripheral T lymphocyte immunity and l-dopamine in patients with Parkinson’s disease. J Biol Regul Homeost Agents 32:687–691PubMed Hu ZX, Song WN, Lu XD, Zhou ML, Shao JH (2018) Peripheral T lymphocyte immunity and l-dopamine in patients with Parkinson’s disease. J Biol Regul Homeost Agents 32:687–691PubMed
14.
Zurück zum Zitat Baba Y, Kuroiwa A, Uitti RJ, Wszolek ZK, Yamada T (2005) Alterations of T-lymphocyte populations in Parkinson disease. Parkinsonism Relat Disord 11:493–498CrossRefPubMed Baba Y, Kuroiwa A, Uitti RJ, Wszolek ZK, Yamada T (2005) Alterations of T-lymphocyte populations in Parkinson disease. Parkinsonism Relat Disord 11:493–498CrossRefPubMed
15.
Zurück zum Zitat Sun C, Zhao Z, Yu W, Mo M, Song C, Si Y, Liu Y (2019) Abnormal subpopulations of peripheral blood lymphocytes are involved in Parkinson’s disease. Ann Transl Med 7:637CrossRefPubMedPubMedCentral Sun C, Zhao Z, Yu W, Mo M, Song C, Si Y, Liu Y (2019) Abnormal subpopulations of peripheral blood lymphocytes are involved in Parkinson’s disease. Ann Transl Med 7:637CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Magistrelli L, Storelli E, Rasini E, Contaldi E, Comi C, Cosentino M, Marino F (2020) Relationship between circulating CD4+ T lymphocytes and cognitive impairment in patients with Parkinson’s disease. Brain Behav Immun 89:668–674CrossRefPubMed Magistrelli L, Storelli E, Rasini E, Contaldi E, Comi C, Cosentino M, Marino F (2020) Relationship between circulating CD4+ T lymphocytes and cognitive impairment in patients with Parkinson’s disease. Brain Behav Immun 89:668–674CrossRefPubMed
17.
Zurück zum Zitat Chen X, Feng W, Ou R, Liu J, Yang J, Fu J, Cao B, Chen Y, Wei Q, Shang H (2021) Evidence for peripheral immune activation in Parkinson’s disease. Front Aging Neurosci 13:617370CrossRefPubMedPubMedCentral Chen X, Feng W, Ou R, Liu J, Yang J, Fu J, Cao B, Chen Y, Wei Q, Shang H (2021) Evidence for peripheral immune activation in Parkinson’s disease. Front Aging Neurosci 13:617370CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184CrossRefPubMedPubMedCentral Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30:1591–1601CrossRefPubMed Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30:1591–1601CrossRefPubMed
20.
Zurück zum Zitat Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699CrossRefPubMed Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699CrossRefPubMed
21.
Zurück zum Zitat Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296CrossRefPubMed Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296CrossRefPubMed
22.
Zurück zum Zitat Clark DB, Donovan JE (1994) Reliability and validity of the Hamilton Anxiety Rating Scale in an adolescent sample. J Am Acad Child Adolesc Psychiatry 33:354–360CrossRefPubMed Clark DB, Donovan JE (1994) Reliability and validity of the Hamilton Anxiety Rating Scale in an adolescent sample. J Am Acad Child Adolesc Psychiatry 33:354–360CrossRefPubMed
23.
Zurück zum Zitat Stiasny-Kolster K, Mayer G, Schafer S, Moller JC, Heinzel-Gutenbrunner M, Oertel WH (2007) The REM sleep behavior disorder screening questionnaire–a new diagnostic instrument. Mov Disord 22:2386–2393CrossRefPubMed Stiasny-Kolster K, Mayer G, Schafer S, Moller JC, Heinzel-Gutenbrunner M, Oertel WH (2007) The REM sleep behavior disorder screening questionnaire–a new diagnostic instrument. Mov Disord 22:2386–2393CrossRefPubMed
24.
Zurück zum Zitat Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 25:2649–2653CrossRefPubMed Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 25:2649–2653CrossRefPubMed
25.
Zurück zum Zitat Jankovic J, McDermott M, Carter J, Gauthier S, Goetz C, Golbe L, Huber S, Koller W, Olanow C, Shoulson I et al (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology 40:1529–1534CrossRefPubMed Jankovic J, McDermott M, Carter J, Gauthier S, Goetz C, Golbe L, Huber S, Koller W, Olanow C, Shoulson I et al (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology 40:1529–1534CrossRefPubMed
26.
Zurück zum Zitat Lindestam Arlehamn CS, Dhanwani R, Pham J, Kuan R, Frazier A, Rezende Dutra J, Phillips E, Mallal S, Roederer M, Marder KS, Amara AW, Standaert DG, Goldman JG, Litvan I, Peters B, Sulzer D, Sette A (2020) alpha-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease. Nat Commun 11:1875CrossRefPubMedPubMedCentral Lindestam Arlehamn CS, Dhanwani R, Pham J, Kuan R, Frazier A, Rezende Dutra J, Phillips E, Mallal S, Roederer M, Marder KS, Amara AW, Standaert DG, Goldman JG, Litvan I, Peters B, Sulzer D, Sette A (2020) alpha-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease. Nat Commun 11:1875CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Tsukita K, Sakamaki-Tsukita H, Takahashi R (2021) Lower circulating lymphocyte count predicts ApoE ε4-related cognitive decline in Parkinson’s disease. Mov Disord 36:2969–2971CrossRefPubMedPubMedCentral Tsukita K, Sakamaki-Tsukita H, Takahashi R (2021) Lower circulating lymphocyte count predicts ApoE ε4-related cognitive decline in Parkinson’s disease. Mov Disord 36:2969–2971CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Singhania A, Pham J, Dhanwani R, Frazier A, Rezende Dutra J, Marder KS, Phillips E, Mallal S, Amara AW, Standaert DG, Sulzer D, Peters B, Sette A, Lindestam Arlehamn CS (2021) The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse. Sci Rep 11:302CrossRefPubMedPubMedCentral Singhania A, Pham J, Dhanwani R, Frazier A, Rezende Dutra J, Marder KS, Phillips E, Mallal S, Amara AW, Standaert DG, Sulzer D, Peters B, Sette A, Lindestam Arlehamn CS (2021) The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse. Sci Rep 11:302CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134CrossRefPubMed Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134CrossRefPubMed
30.
Zurück zum Zitat Yan Z, Yang W, Wei H, Dean MN, Standaert DG, Cutter GR, Benveniste EN, Qin H (2021) Dysregulation of the adaptive immune system in patients with early-stage Parkinson disease. Neurology(R) Neuroimmunol NEUROINFLAMM 8:e1036CrossRef Yan Z, Yang W, Wei H, Dean MN, Standaert DG, Cutter GR, Benveniste EN, Qin H (2021) Dysregulation of the adaptive immune system in patients with early-stage Parkinson disease. Neurology(R) Neuroimmunol NEUROINFLAMM 8:e1036CrossRef
31.
Zurück zum Zitat Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, Liong C, McMurtrey C, Hildebrand WH, Mao X, Dawson VL, Dawson TM, Oseroff C, Pham J, Sidney J, Dillon MB, Carpenter C, Weiskopf D, Phillips E, Mallal S, Peters B, Frazier A, Lindestam Arlehamn CS, Sette A (2017) T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature 546:656–661CrossRefPubMedPubMedCentral Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, Liong C, McMurtrey C, Hildebrand WH, Mao X, Dawson VL, Dawson TM, Oseroff C, Pham J, Sidney J, Dillon MB, Carpenter C, Weiskopf D, Phillips E, Mallal S, Peters B, Frazier A, Lindestam Arlehamn CS, Sette A (2017) T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature 546:656–661CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Williams-Gray CH, Wijeyekoon R, Yarnall AJ, Lawson RA, Breen DP, Evans JR, Cummins GA, Duncan GW, Khoo TK, Burn DJ, Barker RA, group I-Ps (2016) Serum immune markers and disease progression in an incident Parkinson’s disease cohort (ICICLE-PD). Mov Disord 31:995–1003CrossRefPubMedPubMedCentral Williams-Gray CH, Wijeyekoon R, Yarnall AJ, Lawson RA, Breen DP, Evans JR, Cummins GA, Duncan GW, Khoo TK, Burn DJ, Barker RA, group I-Ps (2016) Serum immune markers and disease progression in an incident Parkinson’s disease cohort (ICICLE-PD). Mov Disord 31:995–1003CrossRefPubMedPubMedCentral
Metadaten
Titel
Association between peripheral adaptive immune markers and disease progression in Parkinson's disease
verfasst von
Yi Xiao
Qianqian Wei
Ruwei Ou
Tianmi Yang
Qirui Jiang
Yanbing Hou
Lingyu Zhang
Kuncheng Liu
Shichan Wang
Junyu Lin
Bi Zhao
Wei Song
Xueping Chen
Ying Wu
Chunyu Li
Huifang Shang
Publikationsdatum
06.06.2023
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 9/2023
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-023-11790-3

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