Journal of Parkinson's Disease - Volume Pre-press, issue Pre-press

Authors: Kung, Pin-Jui | Elsayed, Inas | Reyes-Pérez, Paula | Bandres-Ciga, Sara

Article Type: Review Article

Abstract: Parkinson’s disease (PD) is increasingly recognised as a systemic disorder in which inflammation might play a causative role rather than being a consequence or an epiphenomenon of the neurodegenerative process. Although growing genetic evidence links the central and peripheral immune system with both monogenic and sporadic PD, our understanding on how the immune system contributes to PD pathogenesis remains a daunting challenge. In this review, we discuss recent literature aimed at exploring the role of known genes and susceptibility loci to PD pathogenesis through immune system related mechanisms. Furthermore, we outline shared genetic etiologies and interrelations between PD and autoimmune …diseases and underlining challenges and limitations faced in the translation of relevant allelic and regulatory risk loci to immune-pathological mechanisms. Lastly, with the field of immunogenetics expanding rapidly, we place these insights into a future context highlighting the prospect of immune modulation as a promising disease-modifying strategy. Show more

Keywords: Parkinson’s disease, immune system, immunogenetics, risk, onset, progression

DOI: 10.3233/JPD-223176

Citation: Journal of Parkinson's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2022

Authors: Hobson, Benjamin D. | Sulzer, David

Article Type: Review Article

Abstract: Patients with Parkinson’s disease (PD) and other synucleinopathies often exhibit autoimmune features, including CD4+ and some CD8+ T lymphocytes that recognize epitopes derived from alpha-synuclein. While neurons have long been considered to not present antigens, recent data indicate that they can be induced to do so, particularly in response to interferons and other forms of stress. Here, we review literature on neuronal antigen presentation and its potential role in PD. Although direct evidence for CD8+ T cell-mediated neuronal death is lacking in PD, neuronal antigen presentation appears central to the pathology of Rasmussen’s encephalitis, a pediatric neurological …disorder driven by cytotoxic T cell infiltration and neuroinflammation. Emerging data suggest that T cells enter the brain in PD and other synucleinopathies, where the majority of neuromelanin-containing substantia nigra and locus coeruleus neurons express MHC Class I molecules. In cell culture, CD8+ T cell recognition of antigen:MHC Class I complexes on neuronal membranes leads to cytotoxic responses and neuronal cell death. Recent animal models suggest the possibility of T cell autoreactivity to mitochondrial antigens in PD. It remains unclear if neuronal antigen presentation plays a role in PD or other neurodegenerative disorders, and efforts are underway to better elucidate the potential impact of autoimmune responses on neurodegeneration. Show more

Keywords: MHC, HLA, antigen, epitope, T cell, dopamine neurons, Parkinson’s disease

DOI: 10.3233/JPD-223153

Citation: Journal of Parkinson's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Contaldi, Elena | Magistrelli, Luca | Comi, Cristoforo

Article Type: Review Article

Abstract: T cells are key mediators of both humoral and cellular adaptive immune responses, and their role in Parkinson’s disease (PD) is being increasingly recognized. Several lines of evidence have highlighted how T cells are involved in both the central nervous system and the periphery, leading to a profound imbalance in the immune network in PD patients. This review discusses the involvement of T cells in both preclinical and clinical studies, their importance as feasible biomarkers of motor and non-motor progression of the disease, and recent therapeutic strategies addressing the modulation of T cell response.

Keywords: Parkinson’s disease, T cells, CD4 + T cells, CD8 + T cells, neuroinflammation, peripheral immunity

DOI: 10.3233/JPD-223152

Citation: Journal of Parkinson's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Santos García, Diego | de Deus Fonticoba, Teresa | Cores, Carlos | Castro, Ester Suárez | Hernández Vara, Jorge | Jesús, Silvia | Mir, Pablo | Cosgaya, Marina | Martí, Maria José | Pastor, Pau | Cabo, Iria | Seijo, Manuel | Legarda, Inés | Vives, Bárbara | Caballol, Nuria | Rúiz Martínez, Javier | Croitoru, Ioana | Cubo, Esther | Miranda, Javier | Alonso Losada, Maria Gema | Labandeira, Carmen | López Ariztegui, Nuria | Morales-Casado, Mabel | González Aramburu, Isabel | Infante, Jon | Escalante, Sonia | Bernardo, Noemí | Blázquez Estrada, Marta | Menéndez González, Manuel | Caldentey, Juan García | Borrué, Carmen | Vela, Lydia | Catalán, Maria José | Gómez Mayordomo, Víctor | Kurtis, Mónica | Prieto, Cristina | Ordás, Carlos | Nogueira, Víctor | López Manzanares, Lydia | Ávila Rivera, Maria Asunción | Puente, Victor | García Moreno, Jose Manuel | Solano Vila, Berta | Álvarez Sauco, María | Carrillo Padilla, Francisco | Carlos Martínez Castrillo, Juan | Sánchez Alonso, Pilar | Gastón, Itziar | Kulisevsky, Jaime | Valero, Caridad | de Fábregues, Oriol | González Ardura, Jessica | López Díaz, Luis Manuel | Martinez-Martin, Pablo | COPPADIS Study Group

Article Type: Research Article

Abstract: Background: There is a need for identifying risk factors for hospitalization in Parkinson’s disease (PD) and also interventions to reduce acute hospital admission. Objective: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. Methods: PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed …on time to hospital encounter 1-year after the baseline visit. Results: Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065–5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319–6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757–8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124–4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080–8.322; p = 0.035) was an independent predictor of AH. Conclusion: Falls is an independent predictor of AH in PD patients. Show more

DOI: 10.3233/JPD-212539

Citation: Journal of Parkinson's Disease, vol. Pre-press, no. Pre-press, pp. 1-20, 2021