A Systematic Review and Meta-Analysis of Alpha Synuclein Auto-Antibodies in Parkinson's Disease

Scott, Kirsten M.; Kouli, Antonina; Yeoh, Su L.; Clatworthy, Menna R.; Williams‐Gray, Caroline H.

doi:10.3389/fneur.2018.00815

Cited by 48 publications

(37 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Different antibody isotypes carry out different functions, i.e., IgG but not IgM antibodies can penetrate tissue, where they activate complement and bind Fc receptors on resident macrophages and NK cells to induce antibody-dependent cellular response (38). Total levels of anti-α-syn IgG were the subject of several previous investigations, which yielded discordant results, as reviewed by Scott et al (39). While there was no difference in total anti-α-syn IgG NAb levels between MSA, PD and control groups, we found several significant group differences in IgG subclass levels.…”

Section: Discussionmentioning

confidence: 99%

Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease

et al. 2019

View full text Add to dashboard Cite

Aggregation of alpha-synuclein (α-syn) is considered to be the major pathological hallmark and driving force of Multiple System Atrophy (MSA) and Parkinson's disease (PD). Immune dysfunctions have been associated with both MSA and PD and recently we reported that the levels of natural occurring autoantibodies (NAbs) with high-affinity/avidity toward α-synuclein are reduced in MSA and PD patients. Here, we aimed to evaluate the plasma immunoglobulin (Ig) composition binding α-syn and other amyloidogenic neuropathological proteins, and to correlate them with disease severity and duration in MSA and PD patients. All participants were recruited from a single neurological unit and the plasma samples were stored for later research at the Bispebjerg Movement Disorder Biobank. All patients were diagnosed according to current consensus criteria. Using multiple variable linear regression analyses, we observed higher levels of anti-α-syn IgG1 and IgG3 NAbs in MSA vs. PD, higher levels of anti-α-syn IgG2 NAbs in PD compared to controls, whereas anti-α-syn IgG4 NAbs were reduced in PD compared to MSA and controls. Anti-α-syn IgM levels were decreased in both MSA and PD. Further our data supported that MSA patients' immune system was affected with reduced IgG1 and IgM global levels compared to PD and controls, with further reduced global IgG2 levels compared to PD. These results suggest distinct autoimmune patterns in MSA and PD. These findings suggest a specific autoimmune physiological mechanism involving responses toward α-syn, differing in neurodegenerative disease with overlapping α-syn pathology.

show abstract

Section: Discussionmentioning

confidence: 99%

Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The majority of studies of Igs have focused on changes in the amounts of α-syn antibodies, but the results are inconsistent and contradictory [ 112 , 113 ]. However, a study that measured the affinity of these antibodies revealed that the amount of high-affinity α-syn antibodies in the plasma of PD patients is lower than that in healthy controls, and that there are markedly fewer α-syn–antibody immunocomplexes in the plasma of PD patients.…”

Section: Role Of Igs In Pdmentioning

confidence: 99%

“…Several studies demonstrated that serum α-syn antibody titers in patients are different depending on age, disease duration, severity, and genetic inheritance. The distinct pattern of pathology and symptom progression associated with some isolated naturally occurring human anti-α-syn antibodies might be a potent diagnostic marker for PD [ 65 , 112 , 113 ]. However, a systematic review and meta-analysis highlight many caveats to this conclusion based on the limitations of the assays used, the clinical heterogeneity of the study cohorts, the lack of longitudinal data, and poor matching of controls to patients; thus, the overall quality of the evidence is poor.…”

Section: Role Of Igs In Pdmentioning

confidence: 99%

“…However, a systematic review and meta-analysis highlight many caveats to this conclusion based on the limitations of the assays used, the clinical heterogeneity of the study cohorts, the lack of longitudinal data, and poor matching of controls to patients; thus, the overall quality of the evidence is poor. Hence, the value of α-syn autoantibodies as diagnostic or prognostic biomarkers remains uncertain [ 113 ]. Another study tried to identify changes in a panel of autoantibodies in the blood of PD.…”

Section: Role Of Igs In Pdmentioning

confidence: 99%

See 1 more Smart Citation

The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

Sim

Park

2020

IJMS

View full text Add to dashboard Cite

Natural autoantibodies, immunoglobulins (Igs) that target self-proteins, are common in the plasma of healthy individuals; some of the autoantibodies play pathogenic roles in systemic or tissue-specific autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Recently, the field of autoantibody-associated diseases has expanded to encompass neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), with related studies examining the functions of Igs in the central nervous system (CNS). Recent evidence suggests that Igs have various effects in the CNS; these effects are associated with the prevention of neurodegeneration, as well as induction. Here, we summarize the functional roles of Igs with respect to neurodegenerative disease (AD and PD), focusing on the target antigens and effector cell types. In addition, we review the current knowledge about the roles of these antibodies as diagnostic markers and immunotherapies.

show abstract

“…PD may also have a humoral immune component, as increased IgG antibodies have been found against α-synuclein and dopaminergic neurons in patients with advanced disease. This suggests that antibodies are capable of crossing the BBB during active PD (Sanchez-Guajardo et al, 2013), but the contribution of IgG antibodies to earlier disease stages remains unclear (Scott et al, 2018). Because innate immune responses are critical in determining adaptive immune cell engagement and differentiation, it is possible that many of the T and B cell phenotypes described here occur downstream of innate immune responses following general stresses like mitochondrial damage or infection.…”

Section: Introductionmentioning

confidence: 99%

Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat

Patrick

Bell

Weindel

et al. 2019

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Despite major strides in personalized genomics, it remains poorly understood why neurodegenerative diseases occur in only a fraction of individuals with a genetic predisposition and conversely, why individuals with no genetic risk of a disorder develop one. Chronic diseases like Alzheimer's, Parkinson's, and Multiple sclerosis are speculated to result from a combination of genetic and environmental factors, a concept commonly referred to as the “multiple hit hypothesis.” A number of bacterial infections have been linked to increased risk of neurodegeneration, and in some cases, clearance of bacterial pathogens has been correlated with amelioration of central nervous system (CNS) deficits. Additionally, mutations in several genes known to contribute to CNS disorders like Parkinson's Disease have repeatedly been implicated in susceptibility to intracellular bacterial infection. Recent data has begun to demonstrate roles for these genes ( PARK2, PINK1 , and LRRK2 ) in modulating innate immune outcomes, suggesting that immune dysregulation may play an even more important role in neurodegeneration than previously appreciated. This review will broadly explore the connections between bacterial infection, immune dysregulation, and CNS disorders. Understanding this interplay and how bacterial pathogenesis contributes to the “multiple-hit hypothesis” of neurodegeneration will be crucial to develop therapeutics to effectively treat both neurodegeneration and infection.

show abstract

A Systematic Review and Meta-Analysis of Alpha Synuclein Auto-Antibodies in Parkinson's Disease

Cited by 48 publications

References 46 publications

Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease

Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease

The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat

Contact Info

Product

Resources

About