The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

Sim, Kyu-Young; Im, Kyeong Chan; Park, Sung‐Gyoo

doi:10.3390/ijms21155295

Cited by 19 publications

(13 citation statements)

References 137 publications

(174 reference statements)

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“…This point is further corroborated by the fact that serum autoantibodies alone might occur in healthy humans that do not reveal cognitive decline, as a study by Levin demonstrated (Levin et al 2010 ). In addition, autoantibodies may not even contribute to the disease progress and pathophysiology, as they can play a protective role, i.e., specific autoantibodies in Alzheimer’s disease (Sim et al 2020 ). Another relevant issue is that the presence of serum autoantibodies seems to depend on the blood–brain barrier’s integrity, as its breakdown is accompanied by the numerous and highly varied human brain reactive autoantibodies targeting membrane proteins (Levin et al 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Neural cell-surface and intracellular autoantibodies in patients with cognitive impairment from a memory clinic cohort

et al. 2021

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Autoantibody-associated cognitive impairment is an expanding field in geriatric psychiatry. We aim to assess the association between the presence of specific neural autoantibodies and cognitive performance in a memory clinic cohort. 154 patients with cognitive impairment were included between 2019 and 2020 presenting initially in a memory clinic. We evaluated their patient files retrospectively applying epidemiologic parameters, psychopathology, neuropsychology, intracellular and membrane-surface autoantibodies in serum and cerebrospinal fluid (CSF) and markers of neurodegeneration in CSF. In 26 of 154 patients, we searched for neural autoantibodies due to indicators for autoimmunity. In 15/26 (58%) of patients we detected serum and/or CSF autoantibodies. We identified autoantibodies against intracellular or cell-surface antigens in 7 of all 26 (27%) patients with cognitive dysfunction, although we cannot exclude patients with potential specific autoantibodies lacking autoimmune indicators. There were no significant differences between psychopathological and neuropsychological profiles in groups of patients with cognitive impairment comprising patients with autoantibodies (ABS + COG), no autoantibodies (ABS − COG), and Alzheimer’s disease (ADCOG). Concerning our CSF parameters, we detected intrathecal IgG synthesis in 14% of ABS + COG and in 13% of ABS − COG patients, whereas no intrathecal IgG synthesis was found in ADCOG patients. Furthermore, CSF Aß42 was significantly diminished in the ADCOG compared to the ABS + COG group (p < 0.05). In addition, the Aß42/40 ratio was lower in ADCOG patients than in the ABS + COG or ABS − COG group (p < 0.05). Our findings reveal the underestimated occurrence and autoantibodies’ potential role in patients presenting cognitive impairment. Furthermore, the patients with possible Alzheimer’s disease might be differentiated from autoantibody-positive patients via a reduced Aß42 and Aß42/40 ratio in the CSF. The antibody-type varies between patients to a relevant degree, thus demonstrating the need for more research to identify subgroup-specific phenotypes. These pilot study results open an avenue for improving diagnosis and treatment in a memory clinic.

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Section: Discussionmentioning

confidence: 99%

Neural cell-surface and intracellular autoantibodies in patients with cognitive impairment from a memory clinic cohort

et al. 2021

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“…The vascular-derived anti-neuronal autoantibodies contained in specific brain neurons with degenerative and apoptotic features, including C1q and C5b-9 complement compounds and the permeable blood brain barrier, suggest autoimmunity-induced cell death in AD [ 112 ]. More specifically, autoantibodies targeting FcγR-mediated function, tau and ceramide in AD or FcγR-mediated function in PD, were observed to be pathogenic [ 113 ]. Most recently, putative 16 autoantibody biomarkers were detected in the cerebrospinal fluid of AD [ 114 ] So, not surprising is the above mentions gluten-brain cross-reactivity [ 8 , 9 , 10 , 78 , 79 ] and sequence homology between gluten/gliadin peptides and cephalic epitopes ( Table 3 ).…”

Section: Discussionmentioning

confidence: 99%

“Let Food Be Thy Medicine”: Gluten and Potential Role in Neurodegeneration

Lerner

Benzvi

2021

Cells

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Wheat is a most favored staple food worldwide and its major protein is gluten. It is involved in several gluten dependent diseases and lately was suggested to play a role in non-celiac autoimmune diseases. Its involvement in neurodegenerative conditions was recently suggested but no cause-and-effect relationship were established. The present narrative review expands on various aspects of the gluten-gut-brain axes events, mechanisms and pathways that connect wheat and gluten consumption to neurodegenerative disease. Gluten induced dysbiosis, increased intestinal permeabillity, enteric and systemic side effects, cross-reactive antibodies, and the sequence of homologies between brain antigens and gluten are highlighted. This combination may suggest molecular mimicry, alluding to some autoimmune aspects between gluten and neurodegenerative disease. The proverb of Hippocrates coined in 400 BC, “let food be thy medicine,” is critically discussed in the frame of gluten and potential neurodegeneration evolvement.

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“…The arrival of peripheral immune cells at the CNS may have a role in modulating these microglial functions such that subsequent stimuli produce exaggerated responses, and thus affect the outcome in CNS injury and disease (Prinz and Priller, 2017 ; Greenhalgh et al, 2020 ; Urban et al, 2020 ). All lines of evidence provided, it might be speculated that a key trigger to PD pathogenesis is the peripheral immune system that could affect the neuroinflammation of CNS to induce and promote the process of PD (Sim et al, 2020 ). In this study, using high throughput data and bioinformatic techniques, we provided more robust evidence for the potential roles of infiltrating immunocytes in PD as well as their key molecules, which might be helpful to further illustrate the correlations between the peripheral immune system and PD.…”

Section: Discussionmentioning

confidence: 99%

Immune Profiling of Parkinson’s Disease Revealed Its Association With a Subset of Infiltrating Cells and Signature Genes

Zhang

Shao

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is an age-related and second most common neurodegenerative disorder. In recent years, increasing evidence revealed that peripheral immune cells might be able to infiltrate into brain tissues, which could arouse neuroinflammation and aggravate neurodegeneration. This study aimed to illuminate the landscape of peripheral immune cells and signature genes associated with immune infiltration in PD. Several transcriptomic datasets of substantia nigra (SN) from the Gene Expression Omnibus (GEO) database were separately collected as training cohort, testing cohort, and external validation cohort. The immunoscore of each sample calculated by single-sample gene set enrichment analysis was used to reflect the peripheral immune cell infiltration and to identify the differential immune cell types between PD and healthy participants. According to receiver operating characteristic (ROC) curve analysis, the immunoscore achieved an overall accuracy of the area under the curve (AUC) = 0.883 in the testing cohort, respectively. The immunoscore displayed good performance in the external validation cohort with an AUC of 0.745. The correlation analysis and logistic regression analysis were used to analyze the correlation between immune cells and PD, and mast cell was identified most associated with the occurrence of PD. Additionally, increased mast cells were also observed in our in vivo PD model. Weighted gene co-expression network analysis (WGCNA) was used to selected module genes related to a mast cell. The least absolute shrinkage and selection operator (LASSO) analysis and random-forest analysis were used to analyze module genes, and two hub genes RBM3 and AGTR1 were identified as associated with mast cells in the training cohort. The expression levels of RBM3 and AGTR1 in these cohorts and PD models revealed that these hub genes were significantly downregulated in PD. Moreover, the expression trend of the aforementioned two genes differed in mast cells and dopaminergic (DA) neurons. In conclusion, this study not only exhibited a landscape of immune infiltrating patterns in PD but also identified mast cells and two hub genes associated with the occurrence of PD, which provided potential therapeutic targets for PD patients (PDs).

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The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

Cited by 19 publications

References 137 publications

Neural cell-surface and intracellular autoantibodies in patients with cognitive impairment from a memory clinic cohort

Neural cell-surface and intracellular autoantibodies in patients with cognitive impairment from a memory clinic cohort

“Let Food Be Thy Medicine”: Gluten and Potential Role in Neurodegeneration

Immune Profiling of Parkinson’s Disease Revealed Its Association With a Subset of Infiltrating Cells and Signature Genes

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