| 1. |
- Ahlgren, Erika, et al.
(författare)
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Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
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| 2. |
- Anesten, Birgitta, et al.
(författare)
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Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV.
- 2016
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Ingår i: Neurology, Neuroimmunology & Neuroinflammation. - 2332-7812. ; 3:6
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Tidskriftsartikel (refereegranskat)abstract
- Although blood-brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined.BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART).The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis.BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals.
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| 3. |
- Edén, Arvid, 1975, et al.
(författare)
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Asymptomatic Cerebrospinal Fluid HIV-1 Viral Blips and Viral Escape During Antiretroviral Therapy: A Longitudinal Study.
- 2016
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 214:12, s. 1822-1825
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Tidskriftsartikel (refereegranskat)abstract
- We examined longitudinal cerebrospinal fluid (CSF) samples (median, 5 samples/patients; interquartile range [IQR], 3-8 samples/patient) in 75 neurologically asymptomatic human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy. Twenty-seven patients (36%) had ≥1 CSF HIV RNA load of >20 copies/mL (23% had ≥1 load of >50 copies/mL), with a median HIV RNA load of 50 copies/mL (IQR, 32-77 copies/mL). In plasma, 42 subjects (52%) and 22 subjects (29%) had an HIV RNA load of >20 and >50 copies/mL, respectively. Two subjects had an increasing virus load in consecutive CSF samples, representing possible CSF escape. Of 418 samples, 9% had a CSF HIV RNA load of >20 copies/mL (5% had a load of >50 copies/mL) and 19% had a plasma HIV RNA load of >20 copies/mL (8% had a load of >50 copies/mL). A CSF-associated virus load of >20 copies/mL was associated with higher CSF level of neopterin. In conclusion, CSF escape was rare, and increased CSF HIV RNA loads usually represented CSF virus load blips.
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| 4. |
- Edén, Arvid, 1975, et al.
(författare)
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HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.
- 2010
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 202:12, s. 1819-25
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Tidskriftsartikel (refereegranskat)abstract
- Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank.
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| 5. |
- Edén, Arvid, 1975, et al.
(författare)
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Reply to Seligman
- 2011
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Ingår i: J Infect Dis. ; 2011:1, s. 174-175
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Edén, Arvid, 1975, et al.
(författare)
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Residual Central Nervous System Immune Activation Is Not Prevented by Antiretroviral Therapy Initiated During Early Chronic HIV Infection
- 2023
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Antiretroviral therapy (ART) initiated during acute infection can potentially impact the central nervous system (CNS) reservoir, but the differential long-term effects of ART initiation during early or late chronic infection are unknown. Methods We included neuroasymptomatic people with human immunodeficiency virus (HIV) with suppressive ART initiated during chronic (>1 year since transmission) HIV with archived cerebrospinal fluid (CSF) and serum samples after 1 and/or >= 3 years of ART from a cohort study. CSF and serum neopterin was measured using a commercial immunoassay (BRAHMS, Germany). Results In total, 185 people with HIV (median, 79 [interquartile range, 55-128] months on ART) were included. A significant inverse correlation was found between CD4(+) T-cell count and CSF neopterin only at baseline (r = -0.28, P = .002), but not after 1 (r = -0.026, P = .8) or >= 3 (r -0.063, P = .5) years of ART. No significant differences were seen in CSF or serum neopterin concentrations between different pretreatment CD4(+) T-cell strata after 1 or >= 3 (median, 6.6) years of ART. Conclusions In people with HIV initiating ART during chronic infection, occurrence of residual CNS immune activation was not correlated with pretreatment immune status, even when treatment was initiated at high CD4(+) T-cell counts, suggesting that the CNS reservoir, once established, is not differentially affected by the timing of ART initiation during chronic infection.
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| 7. |
- Edén, Arvid, 1975, et al.
(författare)
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Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms.
- 2022
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF).To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity.This cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and prepandemic control groups were included.SARS-CoV-2 infection.Outcomes included CSF SARS-CoV-2 nucleocapsid antigen (N-Ag) using an ultrasensitive antigen capture immunoassay platform and CSF biomarkers of immune activation (neopterin, β2-microglobulin, and cytokines) and neuronal injury (neurofilament light protein [NfL]).Forty-four patients (median [IQR] age, 57 [48-69] years; 30 [68%] male; 26 with moderate COVID-19 and 18 with severe COVID-19 based on the World Health Organization Clinical Progression Scale), 10 healthy controls (median [IQR] age, 58 [54-60] years; 5 [50%] male), and 41 patient controls (COVID negative without evidence of CNS infection) (median [IQR] age, 59 [49-70] years; 19 [46%] male) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r=0.38; P=.03) and interferon γ (r=0.42; P=.01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, β2-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P=.03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P=.04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P=.002). No differences were seen in any CSF biomarkers in moderate compared with severe disease.In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.
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| 8. |
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| 9. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
- 2016
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 3, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. Methods: To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. Findings: Plasma and CSF NFL concentrations were very highly correlated (r=0.89, P<0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4+ T cells. Interpretation: These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings.
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| 10. |
- Grahn, Anna, 1973, et al.
(författare)
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Cerebrospinal fluid biomarkers in patients with varicella-zoster virus CNS infections.
- 2013
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 260:7, s. 1813-1821
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Tidskriftsartikel (refereegranskat)abstract
- Varicella-zoster virus (VZV) is one of our most common viruses causing central nervous system (CNS) infection with sometimes severe neurological complications. Glial fibrillary acidic protein (GFAp), light subunit of neurofilament protein (NFL) and S-100β protein are cerebrospinal fluid (CSF) biomarkers that have been used to estimate the severity of brain damage and outcome in various CNS diseases. So far, these biomarkers have not been utilised to investigate glial pathology and neuronal damage in patients with VZV CNS infections. In this prospective study, we measured CSF GFAp, NFL and S-100β as markers of brain damage in 24 patients with acute neurological manifestations and VZV DNA detected in CSF by PCR and compared with a control group (n=14). Concentrations of CSF NFL and GFAp were increased in patients with VZV CNS infection compared with controls (p=0.002 and p=0.03) while levels of S-100β were reduced. In patients with VZV encephalitis the elevations of CSF NFL and GFAp were more pronounced compared with patients with other VZV CNS syndromes. No correlations between the levels of biomarkers and viral load, neurological sequels or clinical outcome were found in this limited number of patients. These results indicate that VZV induces neuronal damage and astrogliosis with more severe brain damage in patients with VZV encephalitis than in patients with other neurological complications caused by this virus.
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