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  1. Article: PINK1 is a target of T cell responses in Parkinson's disease.

    Williams, Gregory P / Michaelis, Tanner / Lima-Junior, João Rodrigues / Frazier, April / Tran, Ngan K / Phillips, Elizabeth J / Mallal, Simon A / Litvan, Irene / Goldman, Jennifer G / Alcalay, Roy N / Sidney, John / Sulzer, David / Sette, Alessandro / Lindestam Arlehamn, Cecilia S

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Parkinson's disease (PD) is associated with autoimmune T cells that recognize the protein alpha-synuclein in a subset of individuals. Multiple neuroantigens are targets of autoinflammatory T cells in classical central nervous system autoimmune diseases ... ...

    Abstract Parkinson's disease (PD) is associated with autoimmune T cells that recognize the protein alpha-synuclein in a subset of individuals. Multiple neuroantigens are targets of autoinflammatory T cells in classical central nervous system autoimmune diseases such as multiple sclerosis (MS). Here, we explored whether additional autoantigenic targets of T cells in PD. We generated 15-mer peptide pools spanning several PD-related proteins implicated in PD pathology, including GBA, SOD1, PINK1, parkin, OGDH, and LRRK2. Cytokine production (IFNγ, IL-5, IL-10) against these proteins was measured using a fluorospot assay and PBMCs from patients with PD and age-matched healthy controls. This approach identified unique epitopes and their HLA restriction from the mitochondrial-associated protein PINK1, a regulator of mitochondrial stability, as an autoantigen targeted by T cells. The T cell reactivity was predominantly found in male patients with PD, which may contribute to the heterogeneity of PD. Identifying and characterizing PINK1 and other autoinflammatory targets may lead to antigen-specific diagnostics, progression markers, and/or novel therapeutic strategies for PD.
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.09.579465
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Transcriptional analysis of peripheral memory T cells reveals Parkinson's disease-specific gene signatures.

    Dhanwani, Rekha / Lima-Junior, João Rodrigues / Sethi, Ashu / Pham, John / Williams, Gregory / Frazier, April / Xu, Yaqian / Amara, Amy W / Standaert, David G / Goldman, Jennifer G / Litvan, Irene / Alcalay, Roy N / Peters, Bjoern / Sulzer, David / Arlehamn, Cecilia S Lindestam / Sette, Alessandro

    NPJ Parkinson's disease

    2022  Volume 8, Issue 1, Page(s) 30

    Abstract: Parkinson's disease (PD) is a multi-stage neurodegenerative disorder with largely unknown etiology. Recent findings have identified PD-associated autoimmune features including roles for T cells. To further characterize the role of T cells in PD, we ... ...

    Abstract Parkinson's disease (PD) is a multi-stage neurodegenerative disorder with largely unknown etiology. Recent findings have identified PD-associated autoimmune features including roles for T cells. To further characterize the role of T cells in PD, we performed RNA sequencing on PBMC and peripheral CD4 and CD8 memory T cell subsets derived from PD patients and age-matched healthy controls. When the groups were stratified by their T cell responsiveness to alpha-synuclein (α-syn) as a proxy for an ongoing inflammatory autoimmune response, the study revealed a broad differential gene expression profile in memory T cell subsets and a specific PD associated gene signature. We identified significant enrichment of transcriptomic signatures previously associated with PD, including for oxidative stress, phosphorylation, autophagy of mitochondria, cholesterol metabolism and inflammation, and the chemokine signaling proteins CX3CR1, CCR5, and CCR1. In addition, we identified genes in these peripheral cells that have previously been shown to be involved in PD pathogenesis and expressed in neurons, such as LRRK2, LAMP3, and aquaporin. Together, these findings suggest that features of circulating T cells with α-syn-specific responses in PD patients provide insights into the interactive processes that occur during PD pathogenesis and suggest potential intervention targets.
    Language English
    Publishing date 2022-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2819218-7
    ISSN 2373-8057
    ISSN 2373-8057
    DOI 10.1038/s41531-022-00282-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Autologous Hematopoietic Stem Cell Transplantation for Autoimmune Diseases: From Mechanistic Insights to Biomarkers.

    Malmegrim, Kelen Cristina Ribeiro / Lima-Júnior, João Rodrigues / Arruda, Lucas Coelho Marlière / de Azevedo, Júlia Teixeira Cottas / de Oliveira, Gislane Lelis Vilela / Oliveira, Maria Carolina

    Frontiers in immunology

    2018  Volume 9, Page(s) 2602

    Abstract: Phase I/II clinical trials of autologous hematopoietic stem cell transplantation (AHSCT) have led to increased safety and efficacy of this therapy for severe and refractory autoimmune diseases (AD). Recent phase III randomized studies have demonstrated ... ...

    Abstract Phase I/II clinical trials of autologous hematopoietic stem cell transplantation (AHSCT) have led to increased safety and efficacy of this therapy for severe and refractory autoimmune diseases (AD). Recent phase III randomized studies have demonstrated that AHSCT induces long-term disease remission in most patients without any further immunosuppression, with superior efficacy when compared to conventional treatments. Immune monitoring studies have revealed the regeneration of a self-tolerant T and B cell repertoire, enhancement of immune regulatory mechanisms, and changes toward an anti-inflammatory milieu in patients that are responsive to AHSCT. However, some patients reactivate the disease after transplantation due to reasons not yet completely understood. This scenario emphasizes that additional specific immunological interventions are still required to improve or sustain therapeutic efficacy of AHSCT in patients with AD. Here, we critically review the current knowledge about the operating immune mechanisms or established mechanistic biomarkers of AHSCT for AD. In addition, we suggest recommendations for future immune monitoring studies and biobanking to allow discovery and development of biomarkers. In our view, AHSCT for AD has entered a new era and researchers of this field should work to identify robust predictive, prognostic, treatment-response biomarkers and to establish new guidelines for immune monitoring studies and combined therapeutic interventions to further improve the AHSCT protocols and their therapeutic efficacy.
    MeSH term(s) Animals ; Autoimmune Diseases/therapy ; Biomarkers/metabolism ; Biomarkers, Pharmacological/metabolism ; Clinical Trials as Topic ; Combined Modality Therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Monitoring, Immunologic ; Practice Guidelines as Topic ; Self Tolerance ; Transplantation, Autologous
    Chemical Substances Biomarkers ; Biomarkers, Pharmacological
    Language English
    Publishing date 2018-11-16
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.02602
    Database MEDical Literature Analysis and Retrieval System OnLINE

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