| 1. |
- Anderson, Albert M, et al.
(författare)
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Cerebrospinal fluid CXCL10 is associated with the presence of low level CSF HIV during suppressive antiretroviral therapy.
- 2021
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Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 353
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Tidskriftsartikel (refereegranskat)abstract
- Surrogate markers of HIV central nervous system (CNS) persistence are needed because direct HIV measurements from the CNS require specialized protocols and are not always detectable or quantifiable. We analyzed paired plasma and CSF samples from people with HIV (PWH) on suppressive therapy (ART) with a validated HIV single copy RNA assay. Two potential markers of CNS persistence were measured (CXCL10 and sCD30). We then examined associations with CSF HIV RNA positivity in univariable and multivariable analyses. Among 66 individuals, 18.2% had detectable CSF HIV. Individuals who had detectable HIV in CSF had higher CSF CXCL10 concentrations (median 514pg/ml versus median 317pg/ml, p=0.019), but did not have significantly different CSF sCD30 concentrations (median 7.5ng/ml versus median 7.6ng/ml, p=0.78). In the multiple logistic analysis, both higher CSF CXCL10 (p=0.038) and plasma HIV detectability (p=0.035) were significantly associated with detectable CSF HIV. Both sCD30 and CXCL10 correlated positively with NfL and NSE, two neuronal markers. This study demonstrates that CSF CXCL10 concentrations reflect low level HIV CNS persistence despite virologic suppression on ART. Given that it is readily detectable and quantifiable, this chemokine may be a promising biomarker to evaluate HIV eradication therapies that target the CNS.
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| 2. |
- Brune-Ingebretsen, S., et al.
(författare)
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Immune cell subpopulations and serum neurofilament light chain are associated with increased risk of disease worsening in multiple sclerosis
- 2023
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Ingår i: Journal of Neuroimmunology. - 0165-5728. ; 382
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Tidskriftsartikel (refereegranskat)abstract
- Changes is lymphocyte subpopulations in peripheral blood have been proposed as biomarkers for evaluation of disease activity in multiple sclerosis (MS). Serum neurofilament light chain (sNfL) is a biomarker reflecting neuro-axonal injury in MS that could be used to monitor disease activity, response to drugs and to prognosticate disease course. Here we show a moderate correlation between sNfL and lymphocyte cell subpopulations, and our data furthermore suggest that sNfL and specific immune cell subpopulations together could predict future disease worsening in MS.
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| 3. |
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| 4. |
- Cederberg, David, et al.
(författare)
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Prolonged and intense neuroinflammation after severe traumatic brain injury assessed by cerebral microdialysis with 300 kDa membranes
- 2023
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728. ; 377
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Tidskriftsartikel (refereegranskat)abstract
- Background: A neuroinflammatory response that may lead to edema and secondary brain damage is elicited in severe traumatic brain injury (TBI). Previous studies using microdialysis (MD) membranes with 100 k Dalton (kDa) cut-off found a transient intracerebral release of cytokines and chemokines without significant correlations to clinical course, intracranial pressure (ICP) or metabolites. In this study, a (300 kDa) MD probe was used to measure the levels of cytokines and chemokines in relation to ICP and metabolites. Methods: Seven patients with severe TBI received 2 MD catheters. In four patients sufficient dialysate could be retrieved for analysis from both catheters. MD samples were analyzed bedside, then frozen and analyzed for chemokines and cytokines using a multiplex assay (Mesoscale Discovery). Results: MD sampling was performed from 9 to 350 h. In total, 17 chemokines and cytokines were detected. Of these, IL-6, IL-8, IP-10, MCP-1 and MIP-1β were consistently elevated, and investigated further in relation to metabolites, and ICP. Levels of chemokines and cytokines were higher than previously reported from TBI patients, and partially higher than those reported in patients with cytokine release syndrome. There were no significant differences between the two catheters regarding cytokine/chemokine concentrations, except for IL-6 which was higher in the peri-contusional area. No correlation with metabolites and ICP was observed. No significant increase or decline of chemokine or cytokine secretion was observed during the study period. Conclusion: Our data suggest that cytokine and chemokine levels reflect a perpetual, potent and pan-cerebebral inflammatory response that persists beyond 15 days following TBI.
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| 5. |
- Hawes, I. A., et al.
(författare)
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Viral co-infection, autoimmunity, and CSF HIV antibody profiles in HIV central nervous system escape
- 2023
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Ingår i: Journal of Neuroimmunology. - 0165-5728. ; 381
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Tidskriftsartikel (refereegranskat)abstract
- Antiretroviral therapy (ART) suppresses plasma and cerebrospinal fluid (CSF) HIV replication. Neurosymptomatic (NS) CSF escape is a rare exception in which CNS HIV replication occurs in the setting of neurologic impairment. The origins of NS escape are not fully understood. We performed a case-control study of asymptomatic (AS) escape and NS escape subjects with HIV-negative subjects as controls in which we investigated differential immunoreactivity to self-antigens in the CSF of NS escape by employing neuroanatomic CSF immunostaining and massively multiplexed self-antigen serology (PhIP-Seq). Additionally, we utilized pan-viral serology (VirScan) to deeply profile the CSF anti-viral antibody response and metagenomic next-generation sequencing (mNGS) for pathogen detection. We detected Epstein-Barr virus (EBV) DNA more frequently in the CSF of NS escape subjects than in AS escape subjects. Based on immunostaining and PhIP-Seq, there was evidence for increased immunoreactivity against self-antigens in NS escape CSF. Finally, VirScan revealed several immunodominant epitopes that map to the HIV envelope and gag proteins in the CSF of AS and NS escape subjects. Whether these additional inflammatory markers are byproducts of an HIV-driven process or whether they independently contribute to the neuropathogenesis of NS escape will require further study.
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| 6. |
- Hylén, Ulrika, 1977-, et al.
(författare)
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Increased inflammasome activity in markedly ill psychiatric patients : An explorative study
- 2020
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Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 339
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate inflammatory perturbations in 40 patients with severe and complex psychiatric disorders by studying the activity of the NLRP3 inflammasome, with a trans-diagnostic approach. Gene expression of CASP1, NLRP3, PYCARD, IL1B, IL1RN, TNF showed a significant increase in the patient group compared to a matched control group. Plasma levels of IL1Ra, IL-18, TNF, IL-6 and CRP were increased in the patient group. Within the patient group, increased gene expression of inflammatory markers correlated with increased disease severity. The findings support the inflammation hypothesis for markedly ill psychiatric patients across diagnostic groups.
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| 7. |
- Håkansson, Irene, 1976-, et al.
(författare)
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Complement activation in cerebrospinal fluid in clinically isolated syndrome and early stages of relapsing remitting multiple sclerosis
- 2020
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Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 340
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Tidskriftsartikel (refereegranskat)abstract
- To assess if markers of complement activation are associated with disease activity, C1q, C3, C3a and sC5b-9 levels in plasma and cerebrospinal fluid (CSF) were determined in 41 patients with clinically isolated syndrome (CIS) or remitting multiple sclerosis (RRMS), in a prospective longitudinal four-year cohort study. C1q in CSF (CSF-C1q) was significantly higher in patients than in controls. Baseline CSF-C1q and CSF-C3a correlated with several neuroinflammatory markers and neurofilament light chain levels. Baseline CSF-C3a correlated with the number of T2 lesions at baseline and new T2 lesions during follow-up. Baseline CSF-C3a was also significantly higher in patients with (n = 21) than in patients without (n = 20) signs of disease activity according to the NEDA-3 concept during one year of follow-up (p ≤ .01) Study results support that complement activation is involved in MS pathophysiology and that CSF-C3a carries prognostic information.
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| 8. |
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| 9. |
- Johansson, Anton, et al.
(författare)
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Neurological manifestations of COVID-19 : A comprehensive literature review and discussion of mechanisms
- 2021
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Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 358
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Forskningsöversikt (refereegranskat)abstract
- Several neurological symptoms and complications have been described in association with COVID-19, such as anosmia, ageusia, encephalitis and Guillain-Barre ' syndrome. Here, we review the literature describing SARSCoV-2-induced neurological manifestations and provide a comprehensive discussion of proposed mechanisms underlying the neurological pathophysiology. First, we analyse the neuroinvasiveness potential of the coronavirus family based on previous SARS-CoV-1 studies. Then, we describe the current evidence on COVID-19induced nervous tissue damage, including processes behind brain vasculopathy and cytokine storm. We also discuss in detail anosmia and Guillain-Barre ' syndrome. Finally, we provide a summarised timeline of the main findings in the field. Future perspectives are presented, and suggestions of further investigations to clarify how SARS-COV-2 can affect the CNS.
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| 10. |
- Palada, Vinko, et al.
(författare)
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Elevated inflammatory proteins in cerebrospinal fluid from patients with painful knee osteoarthritis are associated with reduced symptom severity
- 2020
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Ingår i: Journal of Neuroimmunology. - : ELSEVIER. - 0165-5728 .- 1872-8421. ; 349
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation and periphery-to-CNS neuroimmune cross-talk in patients with painful knee osteoarthritis (OA) are poorly understood. We utilized proximity extension assay to measure the level of 91 inflammatory proteins in CSF and serum from OA patients and controls. The patients had elevated levels of 48 proteins in CSF indicating neuroinflammation. Ten proteins were correlated between CSF and serum and potentially involved in periphery-to-CNS neuroimmune cross-talk. Seven CSF proteins, all with previously reported neuroprotective effects, were associated with lower pain intensity and milder knee-related symptoms. Our findings indicate that neuroinflammation in OA could be protective and associated with less severe symptoms.
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