Infiltration of immune cells to the brain and its relation to the pathogenesis of Alzheimer's and Parkinson's diseases.

The neurovascular unit, composed of vascular endothelium, vascular smooth muscle, extracellular matrix components, pericytes, astrocytes, microglia, and neurons, allows the highly regulated exchange of molecules and the limited trafficking of cells to the brain through coordinated signaling activity. The passage of peripheral immune cells to the brain parenchyma is observed when there is clear damage to the barriers of this neurovascular unit, as occurs in traumatic brain injury. The possibility of leukocyte infiltration to the brain in neurodegenerative conditions has been proposed. In this review, we focus on describing the evidence for peripheral immune cell infiltration to the brain in the two most frequent neurodegenerative diseases: Alzheimer's and Parkinson's diseases. In particular, we address the mechanisms that promote the passage of these cells into the brain under such pathological conditions. We also discuss the relevance of the resulting cellular interactions, which provide evidence that the presence of peripheral immune cells in the brain is a key point in these neurodegenerative diseases.

Increased levels of regulatory T cells and IL-10-producing regulatory B cells are linked to improved clinical outcome in Parkinson's disease: a 1-year observational study.

Whilst the contribution of peripheral and central inflammation to neurodegeneration in Parkinson's disease and the role of the immune response in this disorder are well known, the effects of the anti-inflammatory response on the disease have not been described in depth. This study is aimed to assess the changes in the regulatory/inflammatory immune response in recently diagnosed, untreated PD patients and a year after. Twenty-one PD patients and 19 healthy controls were included and followed-up for 1 year. The levels of immunoregulatory cells (CD4+ Tregs, Bregs, and CD8+ Tregs); classical, nonclassical, and intermediate monocytes, and proinflammatory cells (Th1, Th2, and Th17) were measured by flow cytometry. Cytokine levels were determined by ELISA. Clinical follow-up was based on the Hoehn & Yahr and UDPRS scales. Our results indicate that the regulatory response in PD patients on follow-up was characterized by increased levels of active Tregs, functional Tregs, TR1, IL-10-producing functional Bregs, and IL-10-producing classical monocytes, along with decreased counts of Bregs and plasma cells. With respect to the proinflammatory immune response, peripheral levels of Th1 IFN-γ+ cells were decreased in treated PD patients, whilst the levels of CD4+ TBET+ cells, HLA-DR+ intermediate monocytes, IL-6, and IL-4 were increased after a 1-year follow-up. Our main finding was an increased regulatory T cell response after a 1-year follow-up and its link with clinical improvement in PD patients. In conclusion, after a 1-year follow-up, PD patients exhibited increased levels of regulatory populations, which correlated with clinical improvement. However, a persistent inflammatory environment and active immune response were observed.

Characterization of excretory/secretory products of the Taenia crassiceps cysticercus involved in the induction of regulatory T cells in vivo.

The ability to modulate the host immune response has allowed some parasites to establish themselves in the tissues of an immunocompetent organism. While some parasite excretion/secretion products (ESPs) were recently reported to induce differentiation of regulatory T cells (Tregs), their identity is not known. This work is aimed to identify and characterize ESPs of Taenia crassiceps cysticerci linked with Treg induction in vivo. ESPs were obtained from cultures of T. crassiceps cysticerci and inoculated in mice, measuring Treg levels by flow cytometry. Proteins in ESPs were analyzed by electrophoresis; then, ESPs were classified as either differential or conserved. Differentially included proteins were MS-sequenced and functionally characterized. Only 4 of 10 ESPs induced Tregs. Proteins with catalytic activity and those involved in immunological processes predominated, supporting the idea that these molecules could play an important role in the induction of Tregs.

Meta-analysis to Implement Alpha-Synuclein in Extracellular Vesicles as a Potential Biomarker for Parkinsons Disease.

Background: In Parkinson's disease (PD), exosomes carry α-synuclein (α-syn), a fibrillar protein aggregates with potential value as a biomarker. Objective: Evidence on blood levels of exosomal α-syn in PD patients and controls was reviewed for their consistency. Methods: Thirty-six studies on exosomal α-syn concentrations in PD were identified in a systematic literature search and meta-analysis. Results: Both raw and ratio-adjusted blood exosomal α-syn levels were consistently higher in PD patients than in controls. The standardized mean difference (SMD) was 1.54 (0.18-2.90, CI95%, p < 0.01) and 1.53 (0.23-2.83, CI95%, p < 0.01), respectively. Conclusion: Our results suggest that exosomal α-syn concentrations could be a useful biomarker for PD.

Increased Tc17 cell levels and imbalance of naïve/effector immune response in Parkinson's disease patients in a two-year follow-up: a case control study.

BACKGROUND: Neuroinflammation has been proved to play a role in dopaminergic neuronal death in Parkinson's disease (PD). This link highlights the relevance of the immune response in the progression of the disease. However, little is known about the impact of peripheral immune response on the disease. This study is aimed to evaluate how immune cell populations change in untreated PD patients followed-up for 2 years. METHODS: Thirty-two patients with no previous treatment (PD-0 yr) and twenty-two healthy subjects (controls) were included in the study. PD patients were sampled 1 and 2 years after the start of the treatment. CD4 T cells (naïve/central memory, effector, and activated), CD8 T cells (activated, central memory, effector memory, NKT, Tc1, Tc2, and Tc17), and B cells (activated, plasma, and Lip-AP) were characterized by flow cytometry. RESULTS: We observed decreased levels of naïve/central memory CD4 and CD8 T cells, Tc1, Tc2, NKT, and plasma cells, and increased levels of effector T cells, activated T cells, and Tc17. CONCLUSIONS: PD patients treated for 2 years showed an imbalance in the naive/effector immune response. Naïve and effector cell levels were associated with clinical deterioration. These populations are also correlated to aging. On the other hand, higher Tc17 levels suggest an increased inflammatory response, which may impact the progression of the disease. Our results highlight the relevant effect of treatment on the immune response, which could improve our management of the disease.

Regulatory impairment in untreated Parkinson's disease is not restricted to Tregs: other regulatory populations are also involved.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Various studies have suggested that the immune response plays a key role in this pathology. While a predominantly pro-inflammatory peripheral immune response has been reported in treated and untreated PD patients, the study of the role of the regulatory immune response has been restricted to regulatory T cells. Other immune suppressive populations have been described recently, but their role in PD is still unknown. This study was designed to analyze the pro and anti-inflammatory immune response in untreated PD patients, with emphasis on the regulatory response. METHODS: Thirty-two PD untreated patients and 20 healthy individuals were included in this study. Peripheral regulatory cells (CD4+Tregs, Bregs, CD8+Tregs, and tolerogenic dendritic cells), pro-inflammatory cells (Th1, Th2, and Th17 cells; active dendritic cells), and classical, intermediate, and non-classical monocytes were characterized by flow cytometry. Plasmatic levels of TNF-α, IFN-γ, IL-6, GM-CSF, IL-12p70, IL-4, IL-13, IL-17α, IL-1ß, IL-10, TGF-ß, and IL-35 were determined by ELISA. RESULTS: Decreased levels of suppressor Tregs, active Tregs, Tr1 cells, IL-10-producer CD8regs, and tolerogenic PD-L1+ dendritic cells were observed. With respect to the pro-inflammatory response, a decrease in IL-17-α and an increase in IL-13 levels were observed. CONCLUSION: A decrease in the levels of regulatory cell subpopulations in untreated PD patients is reported for the first time in this work. These results suggest that PD patients may exhibit a deficient suppression of the pro-inflammatory response, which could contribute to the pathophysiology of the disease.

Expression of Dopamine Receptors in Immune Regulatory Cells.

OBJECTIVE: Parkinson's disease (PD) patients are usually treated with L-dopa and/or dopaminergic agonists, which act by binding five types of dopaminergic receptors (DRD1-DRD5). Peripheral immune cells are known to express dopamine receptors on their membrane surface, and therefore they could be directly affected by the treatment. Regulatory cells are the main modulators of inflammation, but it is not clear whether dopaminergic treatment could affect their functions. While only regulatory T cells (Tregs) have been proved to express dopamine receptors, it is not known whether other regulatory cells such as CD8regs, regulatory B cells (Bregs), tolerogenic dendritic cells, and intermediate monocytes also express them. METHODS: The expression of dopamine receptors in Tregs, CD8regs, Bregs, tolerogenic dendritic cells, and intermediate monocytes was herein evaluated. cDNA from 11 PD patients and 9 control subjects was obtained and analyzed. RESULTS: All regulatory cell populations expressed the genes coding for dopamine receptors, and this expression was further corroborated by flow cytometry. These findings may allow us to propose regulatory populations as possible targets for PD treatment. CONCLUSIONS: This study opens new paths to deepen our understanding on the effect of PD treatment on the cells of the regulatory immune response.

Treatment-Resistant Human Extraparenchymal Neurocysticercosis: An Immune-Inflammatory Approach to Cysticidal Treatment Outcome.

OBJECTIVE: The aim of this study is to analyze the immune-endocrine profile in neurocysticercosis (NC) patients resistant to cysticidal treatment. METHODS: The inflammatory and regulatory responses of 8 resistant NC patients with extraparenchymal parasites and 5 healthy controls were evaluated through flow cytometry. Serum interleukin levels were measured by ELISA and catecholamines levels by high performance liquid chromatography. RESULTS: Higher percentages of Tr1, CD4+CD25+FOXP3+CD127- and CD4+CD45RO+FOXP3HI were found in NC patients compared with healthy controls, but no difference was found in catecholamine levels. Antigen-specific proliferative immune response was observed in NC patients. Neither anti-inflammatory nor pro-inflammatory cytokines showed differences between patients and controls, but IL-6 levels were lower in treatment-resistant NC patients. In addition, TGFß showed a significant negative correlation with dopamine. CONCLUSIONS: Altogether, these results may point to a modulation of the neuroinflammation in these patients that could indirectly favor cysticercal survival in CNS microenvironment.

Understanding host-parasite relationship: the immune central nervous system microenvironment and its effect on brain infections.

The central nervous system (CNS) has been recognized as an immunologically specialized microenvironment, where immune surveillance takes a distinctive character, and where delicate neuronal networks are sustained by anti-inflammatory factors that maintain local homeostasis. However, when a foreign agent such as a parasite establishes in the CNS, a set of immune defences is mounted and several immune molecules are released to promote an array of responses, which ultimately would control the infection and associated damage. Instead, a host-parasite relationship is established, in the context of which a close biochemical coevolution and communication at all organization levels between two complex organisms have developed. The ability of the parasite to establish in its host is associated with several evasion mechanisms to the immune response and its capacity for exploiting host-derived molecules. In this context, the CNS is deeply involved in modulating immune functions, either protective or pathogenic, and possibly in parasitic activity as well, via interactions with evolutionarily conserved molecules such as growth factors, neuropeptides and hormones. This review presents available evidence on some examples of CNS parasitic infections inducing different morbi-mortality grades in low- or middle-income countries, to illustrate how the CNS microenvironment affect pathogen establishment, growth, survival and reproduction in immunocompetent hosts. A better understanding of the influence of the CNS microenvironment on neuroinfections may provide relevant insights into the mechanisms underlying these pathologies.

Progressive Supranuclear Palsy Syndrome: An Overview.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease, commonly observed as a movement disorder in the group of parkinsonian diseases. The term PSP usually refers to PSP-Richardson's syndrome (PSP-RS), the most typical clinical presentation. However, the broad concept of progressive supranuclear palsy syndrome (PSP-S) applies to a set of clinical entities that share a pathophysiological origin and some symptoms. According to its clinical predominance, PSP-S is divided into subtypes. PSP-S has clinical similarities with Parkinson's disease, and both pathologies are classified in the group of parkinsonisms, but they do not share pathophysiological traits. By contrast, the pathophysiology of corticobasal syndrome (CBS) depends on tau expression and shares similarities with PSP-S in both pathophysiology and clinical picture. An involvement of the immune system has been proposed as a cause of neurodegeneration. The role of neuroinflammation in PSP-S has been studied by neuroimaging, among other methods. As it is the case in other neurodegenerative pathologies, microglial cells have been attributed a major role in PSP-S. While various studies have explored the detection and use of possible inflammatory biomarkers in PSP-S, no significant advances have been made in this regard. This review is aimed at highlighting the most relevant information on neuroinflammation and peripheral inflammation in the development and progression of PSP-S, to lay the groundwork for further research on the pathophysiology, potential biomarkers, and therapeutic strategies for PSP-S.

Cysticerci drive dendritic cells to promote in vitro and in vivo Tregs differentiation.

Regulatory T cells (Tregs) play a crucial role in immune homeostasis. Treg induction is a strategy that parasites have evolved to modulate the host's inflammatory environment, facilitating their establishment and permanence. In human Taenia solium neurocysticercosis (NC), the concurrence of increased peripheral and central Treg levels and their capacity to inhibit T cell activation and proliferation support their role in controlling neuroinflammation. This study is aimed at identifing possible mechanisms of Treg induction in human NC. Monocyte-derived dendritic cells (DC) from healthy human donors, cocultivated with autologous CD4(+) naïve cells either in the presence or absence of cysticerci, promoted CD25(high)Foxp3+ Treg differentiation. An increased Treg induction was observed when cysticerci were present. Moreover, an augmentation of suppressive-related molecules (SLAMF1, B7-H1, and CD205) was found in parasite-induced DC differentiation. Increased Tregs and a higher in vivo DC expression of the regulatory molecules SLAMF1 and CD205 in NC patients were also found. SLAMF1 gene was downregulated in NC patients with extraparenchymal cysticerci, exhibiting higher inflammation levels than patients with parenchymal parasites. Our findings suggest that cysticerci may modulate DC to favor a suppressive environment, which may help parasite establishment, minimizing the excessive inflammation, which may lead to tissue damage.

Longitudinal Changes in Mitochondrial DNA Copy Number and Telomere Length in Patients with Parkinson's Disease.

Parkinson's disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, and aging as its biggest risk factors. Mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) are biological aging markers with inconclusive results regarding their association with PD. A case-control study was used to measure TL and mtDNA-CN using qPCR in PBMCs. PD patients were naive at baseline (T0) and followed-up at one (T1) and two (T2) years after the dopaminergic treatment (DRT). Plasmatic cytokines were determined by ELISA in all participants, along with clinical parameters of patients at T0. While TL was shorter in patients vs. controls at all time points evaluated (p < 0.01), mtDNA-CN showed no differences. An increase in mtDNA-CN and TL was observed in treated patients vs. naive ones (p < 0.001). Our statistical model analyzed both aging markers with covariates, showing a strong correlation between them (r = 0.57, p < 0.01), and IL-17A levels positively correlating with mtDNA-CN only in untreated patients (r = 0.45, p < 0.05). TL and mtDNA-CN could be useful markers for monitoring inflammation progression or treatment response in PD. DRT might modulate TL and mtDNA-CN, reflecting a compensatory mechanism to counteract mitochondrial dysfunction in PD, but this needs further investigation.

Efficacy of intravenous immunoglobulin in autoimmune neurological diseases. Literature systematic review and meta-analysis.

BACKGROUND: Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin (IVIg) and plasmapheresis, have shown mixed results in patient improvement. OBJECTIVE: To compare the efficacy of IVIg administration with that of corticosteroids, plasmapheresis, and placebo in autoimmune neurological diseases like Guillain-Barré syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, optic neuritis, and multiple sclerosis. METHODS: A systematic review was performed on the databases PubMed, MEDLINE, Embase, and Cochrane. Controlled, randomized studies comparing the efficacy of IVIg with placebo, plasmapheresis, and/or glucocorticoid administration were selected. Only studies reporting the number of patients who improved after treatment were included, irrespective of language or publication year. In total, 23 reports were included in the meta-analysis study. RESULTS: Our meta-analysis showed a beneficial effect of IVIg administration on patient improvement over placebo (OR = 2.79, CI [95%] = 1.40-5.55, P = 0.01). Meanwhile, IVIg administration showed virtually identical effects to plasmapheresis (OR = 0.83, CI [95%] = 0.45-1.55, P < 0.01). Finally, no significant differences were found in the efficacy of IVIg and glucocorticoid administration (OR = 0.98, Cl [95%] = 0.58-1.68, P = 0.13). CONCLUSION: IVIg can be regarded as a viable therapeutic approach, either as a first- or second-line therapy, and as an adjuvant therapy for autoimmune neurological diseases.

Interferon Lambda 3/4 (IFNλ3/4) rs12979860 Polymorphisms Is Not Associated With Susceptibility to Systemic Lupus Erythematosus, Although It Regulates OASL Expression in Patients With SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex etiology. Various genetic factors are associated with susceptibility to developing SLE and contribute to its onset and progression. Different single-nucleotide polymorphisms (SNPs) have been associated with SLE in several populations. The rs12979860 SNP in interferon lambda 3/4 (IFNλ3/4) is significantly associated with SLE susceptibility in patients negative for nephritis in Taiwanese people, and interferon-stimulated genes (ISGs) are differentially expressed in normal liver by the rs12979860 genotype. This study aimed to investigate whether rs12979860 is associated with the presence of SLE and lupus nephritis in Mexican individuals as well as with the expression of several ISGs in SLE patients. In total, 439 SLE patients and 358 healthy donors were genotyped for rs12979860 using real-time PCR, and allelic discrimination plots were constructed. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated from the venous blood of SLE patients by centrifugation (n = 78). The mRNA levels of 2'-5'-oligoadenylate synthetase like (OASL), myxovirus resistance 1 (MX1), 2'5'-oligoadenylate synthetase 1 (OAS1), interferon-stimulated gene 15 (ISG15) and lymphocyte antigen 6 complex, locus E (LY6E) were determined using real-time PCR. The distributions of rs12979860 genotypes and allele frequencies were compared between SLE patients and healthy donors; case-control analysis revealed that rs12979860 was not associated with SLE susceptibility (OR 1.18, 95% CI 0.97-1.45, p = 0.08) or with the risk for lupus nephritis (OR 0.913, 95% CI 0.590-1.411, p = 0.682). However, OASL expression levels in PBMCs were significantly different between rs12979860 genotypes in SLE patients: median OASL mRNA levels were significantly higher in patients carrying the CC genotype (197.10, IQR 71.10-411.17) than in those with CT/TT genotypes (173.75, IQR 58.80-278.75, p = 0.016). Our results suggest that the SNP rs12979860 does not play a relevant role in susceptibility to SLE in Mexican individuals. However, IFNλ3/4 genotypes appear to be associated with OASL expression in PBMCs from patients with SLE.

Pro- and anti-inflammatory response in neurological disorders associated to anti-glutamate decarboxylase antibodies.

Rare conditions showing psychiatric symptoms and movement disorders have been linked with the presence of anti-glutamate decarboxylase antibodies. Proinflammatory and antiinflammatory immune responses were assessed in patients with neurological disorders associated to anti-glutamic acid decarboxylase antibodies (NDGAD). Immunoregulatory and proinflammatory cell populations were quantified by flow cytometry. No polarization toward Th1, Th2, or Th17 phenotypes was observed in NDGAD patients. Immunoregulatory responses were significantly reduced for Breg, activated Treg, Tr1, and Th3 cells, suggesting a deficient regulatory response, while intermediate monocyte levels were increased. The reduced levels of regulatory T and B cells suggest an impairment in regulatory immune response, while intermediate monocytes could be playing a role in the increased proinflammatory response.

A novel, sequencing-free strategy for the functional characterization of Taenia solium proteomic fingerprint.

The flatworm Taenia solium causes human and pig cysticercosis. When cysticerci are established in the human central nervous system, they cause neurocysticercosis, a potentially fatal disease. Neurocysticercosis is a persisting public health problem in rural regions of Mexico and other developing countries of Latin America, Asia, and Africa, where the infection is endemic. The great variability observed in the phenotypic and genotypic traits of cysticerci result in a great heterogeneity in the patterns of molecules secreted by them within their host. This work is aimed to identify and characterize cysticercal secretion proteins of T. solium cysticerci obtained from 5 naturally infected pigs from Guerrero, Mexico, using 2D-PAGE proteomic analysis. The isoelectric point (IP) and molecular weight (MW) of the spots were identified using the software ImageMaster 2D Platinum v.7.0. Since most secreted proteins are impossible to identify by mass spectrometry (MS) due to their low concentration in the sample, a novel strategy to predict their sequence was applied. In total, 108 conserved and 186 differential proteins were identified in five cysticercus cultures. Interestingly, we predicted the sequence of 14 proteins that were common in four out of five cysticercus cultures, which could be used to design vaccines or diagnostic methods for neurocysticercosis. A functional characterization of all sequences was performed using the algorithms SecretomeP, SignalP, and BlastKOALA. We found a possible link between signal transduction pathways in parasite cells and human cancer due to deregulation in signal transduction pathways. Bioinformatics analysis also demonstrated that the parasite release proteins by an exosome-like mechanism, which could be of biological interest.

Regulatory T Cells as an Escape Mechanism to the Immune Response in Taenia crassiceps Infection.

Murine cysticercosis by Taenia crassiceps is a model for human neurocysticercosis. Genetic and/or immune differences may underlie the higher susceptibility to infection in BALB/cAnN with respect to C57BL/6 mice. T regulatory cells (Tregs) could mediate the escape of T. crassiceps from the host immunity. This study is aimed to investigate the role of Tregs in T. crassiceps establishment in susceptible and non-susceptible mouse strains. Treg and effector cells were quantified in lymphoid organs before infection and 5, 30, 90, and 130 days post-infection. The proliferative response post-infection was characterized in vitro. The expression of regulatory and inflammatory molecules was assessed on days 5 and 30 post-infection. Depletion assays were performed to assess Treg functionality. Significantly higher Treg percentages were observed in BALB/cAnN mice, while increased percentages of activated CD127+ cells were found in C57BL/6 mice. The proliferative response was suppressed in susceptible mice, and Treg proliferation occurred only in susceptible mice. Treg-mediated suppression mechanisms may include IL-10 and TGFß secretion, granzyme- and perforin-mediated cytolysis, metabolic disruption, and cell-to-cell contact. Tregs are functional in BALB/cAnN mice. Therefore Tregs could be allowing parasite establishment and survival in susceptible mice but could play a homeostatic role in non-susceptible strains.

Immunomodulatory effect and clinical outcome in Parkinson's disease patients on levodopa-pramipexole combo therapy: A two-year prospective study.

Parkinson's disease (PD), the second most frequent neurodegenerative disease, has been linked to increased central and peripheral inflammation. Although the response of the immune system to dopaminergic treatment remains to be fully understood, dopaminergic agonists are known to exhibit immunoregulatory properties which may, at least in part, explain their therapeutic effect in PD. This highlights the need of analyzing immune parameters in longitudinal studies on PD patients receiving specific therapeutic regimes. In this work, PD patients were included in a two-year prospective study comparing the effect of levodopa alone and a levodopa/pramipexole combo therapy on several regulatory and pro-inflammatory immune cell populations. We demonstrated that PD patients show decreased circulating levels of several important regulatory subpopulations, as determined by flow cytometry. Notably, when administered alone, levodopa decreased the levels of functional Bregs and SLAMF1+ tolerogenic DCs and increased the levels of total and HLA-DR+ classical monocytes, while the pramipexole/levodopa combo may promote Treg- and tolerogenic DC-mediated regulatory responses. These results suggest that a regime based on levodopa alone may promote a pro-inflammatory-type response in PD patients, but when combined with pramipexole, it promotes a clinically beneficial regulatory-type environment.

Stimulation of the primary anti-HIV antibody response by IFN-alpha in patients with acute HIV-1 infection.

Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV-1 and treated with IFN-alpha2b. Patients with acute HIV-1 infection were randomized to receive antiretroviral therapy alone (Group A, n=60) or combined for 14 weeks with pegylated-IFN-alpha2b (Group B, n=30). Emergence of anti-HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-alpha2b treatment stimulated the production of anti-HIV antibodies. On Week 32, 19 weeks after the last IFN-alpha2b administration, there were 8.5 (6.5-10.0) HIV WB bands (median, interquartile range) in Group B and 7.0 (5.0-10.0) bands in Group A (P=0.054), and band intensities were stronger in Group B (P<0.05 for p18, p24, p34, p40, and p55 HIV antigens). IFN-alpha2b treatment also increased circulating concentrations of the B cell-activating factor of the TNF family (P<0.001) and ex vivo production of IL-12 (P<0.05), reflecting its effect on innate immune cells. Withdrawal of antiretroviral treatment on Week 36 resulted in a lower rebound of HIV replication in Group B than in Group A (P<0.05). Therefore, type I IFNs stimulate the emerging anti-HIV immune response in patients with acute HIV-1 infection, resulting in an improved control of HIV replication. Type I IFNs are thus critical in the development of efficient antiviral immune responses in humans, including the production of antiviral antibodies.

Meta-analysis to Implement Alpha-Synuclein in Extracellular Vesicles as a Potential Biomarker for Parkinson's Disease

ABSTRACT Background: In Parkinson's disease (PD), exosomes carry α-synuclein (α-syn), a fibrillar protein aggregates with potential value as a biomarker. Objective: Evidence on blood levels of exosomal α-syn in PD patients and controls was reviewed for their consistency. Methods: Thirty-six studies on exosomal α-syn concentrations in PD were identified in a systematic literature search and meta-analysis. Results: Both raw and ratio-adjusted blood exosomal α-syn levels were consistently higher in PD patients than in controls. The standardized mean difference (SMD) was 1.54 (0.18-2.90, CI95%, p < 0.01) and 1.53 (0.23-2.83, CI95%, p < 0.01), respectively. Conclusion: Our results suggest that exosomal α-syn concentrations could be a useful biomarker for PD.