Background. Despite its overall efficacy, combined antiretroviral therapy (cART) has failed to control human immunodeficiency virus (HIV) infection of the central nervous system (CNS). New acute and ...chronic neurological complications continue to be reported. Methods. We conducted a retrospective study of 14 HIV-infected patients with documented encephalitis, which was initially attributed to an undetermined origin. Brain magnetic resonance imaging (MRI) uniformly revealed unusual, multiple linear gadolinium-enhanced perivascular lesions. Results. All patients had manifested acute or subacute neurological symptoms; the brain MRIs indicating diffuse brain damage. The mean duration of HIV infection was approximately 10 years, and 8 patients were immunovirologically stable. Cerebrospinal fluid abnormalities with mildly elevated protein and pleocytosis with >90% lymphocytes, predominantly CD8, were found in all but 1 patient. The mean cerebral spinal fluid HIV load was 5949 copies/mL. Six patients reported a minor infection a few days prior to neurological symptoms, 2 patients presented criteria for the immune reconstitution inflammatory syndrome of the CNS, 2 were in virological escape, and 1 developed encephalitis after interruption of cART. Brain biopsies revealed inflammatory encephalitis associated with astrocytic and microglial activation as well as massive perivascular infiltration by polyclonal CD8 + lymphocytes. All patients had been treated with glucocorticosteroids. The long-term therapeutic response varied from excellent, with no sequalae (n = 5), to moderate, with cognitive disorders (n = 4). The mean survival time was 8 years; however, 5 patients died within 13 months of initiation of treatment. Conclusions. CD8 encephalitis in HIV-infected patients receiving cART is a clinical entity that should be added to the list of HIV complications.
•Rapid evaluation of treatment efficacy is needed in case of empirical tuberculosis (TB) treatment.•Innate immune markers were measured in patients with TB who are HIV-negative and ...HIV-positive.•Interleukin-1 receptor antagonist and interferon-γ–induced protein-10 plasma levels decreased as soon as 7 days of TB treatment onset.•It is the first report of an early decrease of markers measured with standard enzyme-linked immunosorbent assay.•Interleukin-1 receptor antagonist-guided management deserves evaluation in empirically treated people with HIV.
Monitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation.
ANRS12394-LILAC-TB was a proof-of-concept prospective study: adults with a rifampicin-susceptible TB who are HIV-negative and HIV-infected documented by a positive Xpert MTB/RIF test were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interferon-γ–induced protein-10 and clusters of differentiation (CD) (scavenging CD163) were measured by commercial enzyme-linked immunosorbent assay kits. A Wilcoxon test for paired data was used for longitudinal comparisons.
A total of 55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10 of 13 participants with HIV: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared with baseline, the IL-1Ra plasma levels significantly decreased as soon as week (W) 1, independent of HIV status (−71% in HIV-positive vs −33% in HIV-negative; P <0.001). The IP-10 plasma levels significantly decreased at W1 and W2 compared with baseline (P <0.0001); however, that decrease was less marked in participants with HIV.
Our findings suggest that measuring IL-1Ra plasma levels with a standard enzyme-linked immunosorbent assay technique at baseline and then 1 week after TB treatment onset could help clinicians to quickly assess TB treatment response.
Huntington disease (HD) is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD has not been elucidated, but weight loss, associated with chorea ...and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. (1)H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA), valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide.
Background Despite control of HIV infection under antiretroviral therapy (ART), immune T-cell activation persists in patients with controlled HIV infection, who are at higher risk of inflammatory ...diseases than the general population. PMNs play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in cases of excessive or misdirected responses. Objective The aim of our study was to analyze PMN functions in 60 ART-treated and controlled HIV-infected patients (viral load, <20 RNA copies/mL; CD4 count, ≥350 cells/mm3 ) with (HIVI group) and without (HIVNI group) diseases related to an inflammatory process and to compare them with 22 healthy control subjects. Methods Flow cytometry was used to evaluate PMN functions in whole-blood conditions. We studied in parallel the activation markers of T lymphocytes and monocytes and the proinflammatory cytokine environment. Results Blood samples from HIV-infected patients revealed basal PMN hyperactivation associated with deregulation of the apoptosis/necrosis equilibrium. Interestingly, this hyperactivation was greater in HIV(I) than HIV(NI) patients and contrasted with a lack of monocyte activation in both groups. The percentage of circulating cells producing IL-17 was also significantly higher in HIV-infected patients than in control subjects and was positively correlated with markers of basal PMN activation. In addition, the detection of IL-22 overproduction in HIV(NI) patients suggests that it might contribute to counteracting chronic inflammatory processes during HIV infection. Conclusions This study thus demonstrates the presence of highly activated PMNs in HIV-infected patients receiving effective ART and the association of these cells with a specific IL-17/IL-22 environment.
Introduction
Evaluation of different cell‐based assays for the study of adaptive immune responses against SARS‐CoV‐2 is crucial for studying long‐term and vaccine‐induced immunity.
Methods
...Enzyme‐linked immunospot assay (ELISpot) and intracellular cytokine staining (ICS) using peptide pools spanning the spike protein and nucleoprotein of SARS‐CoV‐2 were performed in 25 patients who recovered from paucisymptomatic (n = 19) or severe COVID‐19 (n = 6).
Results
The proportion of paucisymptomatic patients with detectable SARS‐CoV‐2 T cells was low, as only 44% exhibit a positive T cell response with the ICS and 67% with the ELISpot. The magnitude of SARS‐CoV‐2 T cell responses was low, both with ICS (median at 0.12% among total T cells) and ELISpot (median at 61 SFCs/million peripheral blood mononuclear cells PBMC) assays. Moreover, T cell responses in paucisymptomatic patients seemed lower than among patients with severe disease. In the paucisymptomatic patients, the two assays were well correlated with 76% of concordant responses and a Cohen's kappa of 55. Furthermore, in four patients SARS‐CoV‐2 T cells were detected by ELISpot but not with ICS. Short‐term culture could improve the detection of specific T cells.
Conclusions
In patients who recovered from paucisymptomatic COVID‐19, the proportion of detectable anti‐SARS‐CoV‐2 responses and their magnitude seemed lower than in patients with more severe symptoms. The ELISpot appeared to be more sensitive than the ICS assay. Short‐term culture revealed that paucisymptomatic patients had nonetheless few SARS‐CoV‐2 T cells at a very low rate in peripheral blood. These data indicate that various ex‐vivo assays may lead to different conclusions about the presence or absence of SARS‐CoV‐2 T cell immunity.
Evaluation of different cell‐based assays for the study of adaptive immune responses against SARS‐CoV‐2 is crucial for studying long‐term and vaccine‐induced immunity. The ELISpot shows a better sensitivity than ICS. Short‐term culture reveals that paucisymptomatic patients have nonetheless few SARS‐CoV‐2 T cells at a very low rate in peripheral blood and prompt us to be cautious on the conclusion of SARS‐CoV‐2 cellular immunity with classical assays.
Immune interventions in HIV infection Carcelain, Guislaine; Autran, Brigitte
Immunological reviews,
07/2013, Letnik:
254, Številka:
1
Journal Article
Recenzirano
Summary
Immune‐based therapy (IBT) interventions have found a window of opportunity within some limitations of the otherwise successful combined antiretroviral therapy (cART). Two major paradigms ...drove immunotherapeutic research to combat human immunodeficiency virus (HIV) infection. First, IBTs were proposed either to help restore CD4+ T‐cell counts in cases of therapeutic failures with cytokines, interleukin‐2 (IL‐2) or IL‐7, or to better control HIV and disease progression during treatment interruptions with anti‐HIV therapeutic candidate vaccines. The most widely used candidates were HIV‐recombinant live vector‐based alone or combined with other vaccine compounds and dendritic cell (DC) therapies. A more recent and current paradigm aims at achieving HIV cure by combining IBT with cART using either cytokines to reactivate virus production in latently infected cells and/or therapeutic immunization to boost HIV‐specific immunity in a ‘shock and kill’ strategy. This review summarizes the rationale, hopes, and mechanisms of successes and failures of these cytokine‐based and vaccine‐based immune interventions. Results from these first series of IBTs have been so far somewhat disappointing in terms of clinical relevance, but have provided lessons that are discussed in light of the future combined strategies to be developed toward an HIV cure.
The Kaposi sarcoma—associated herpesvirus (KSHV)-DNA level was determined in samples from 71 patients with Kaposi sarcoma (KS), 28 patients with multicentric Castleman disease (MCD), and 8 patients ...with primary effusion lymphoma (PEL). KSHV-DNA levels were higher in patients with active KS or MCD than in those with KS or MCD in remission. Among patients with active disease, the highest KSHV-DNA levels were observed in effusion fluid samples from patients with PEL (7.2 log10 copies/150,000 cells), followed by blood samples from patients with MCD and PEL (4.86 and 3.83 log10 copies/150,000 cells, respectively), and the lowest levels were observed in blood samples from patients with KS (2.63 log10 copies/150,000 cells). Determining the KSHV-DNA level may be useful in diagnosing KSHV-associated disease and for following up patients with KS when the development of MCD or PEL is suspected.
Background: Flow cytometry has been the approach of choice for enumerating and documenting CD4-cell decline in HIV monitoring. Beckman Coulter has developed a single platform test for CD4+ T-cell ...lymphocyte count and percentage using PanLeucogating (PLG) technology on the automated AQUIOS flow cytometer (AQUIOS PLG).Objectives: This study compared the performance of AQUIOS PLG with the Flowcare PLG method and performed a reference interval for comparison with those previously published.Methods: The study was conducted between November 2014 and March 2015 at 5 different centres located in Canada; Paris, France; Lyon, France; the United States; and South Africa. Two-hundred and forty samples from HIV-positive adult and paediatric patients were used to compare the performances of AQUIOS PLG and Flowcare PLG on a FC500 flow cytometer (Flowcare PLG) in determining CD4+ absolute count and percentage. A reference interval was determined using 155 samples from healthy, non-HIV adults. Workflow was investigated testing 440 samples over 5 days.Results: Mean absolute and relative count bias between AQUIOS PLG and Flowcare PLG was -41 cells/μL and -7.8%. Upward and downward misclassification at various CD4 thresholds was ≤ 2.4% and ≤ 11.1%. The 95% reference interval (2.5th – 97.5th) for the CD4+ count was 453–1534 cells/μL and the percentage was 30.5% – 63.4%. The workflow showed an average number of HIV samples tested as 17.5 per hour or 122.5 per 8-hour shift for one technician, including passing quality controls.Conclusion: The AQUIOS PLG merges desirable aspects from conventional flow cytometer systems (high throughput, precision and accuracy, external quality assessment compatibility) with low technical operating skill requirements for automated, single platform systems.
Current data suggest that COVID-19 is less frequent in children, with a milder course. However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris ...region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities.
Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ('Kawa-COVID-19'). A historical cohort of 'classical' KD served as a comparator.
Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)). SARS-CoV-2 was detected in 12 cases (69%), while a further three cases had documented recent contact with a quantitative PCR-positive individual (19%). Cardiac involvement included myocarditis in 44% (n=7). Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L. Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment. The Kawa-COVID-19 cohort differed from a comparator group of 'classical' KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004).
Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children. Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19.
NCT02377245.
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