Maraviroc and JC virus-associated immune reconstitution inflammatory syndrome.
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ABSTRACT:
SUBMITTER: Giacomini PS
PROVIDER: S-EPMC5052063 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
Publications
Maraviroc and JC virus-associated immune reconstitution inflammatory syndrome.
Giacomini Paul S PS Rozenberg Ayal A Metz Imke I Araujo David D Arbour Nathalie N Bar-Or Amit A
The New England journal of medicine 20140101 5
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Project description:ObjectiveTo study the outcome of patients with multiple sclerosis (MS) and with natalizumab-associated progressive multifocal leukoencephalopathy (PML) and immune reconstitution inflammatory syndrome (IRIS).MethodsMedWatch reports from Biogen-Idec (manufacturer of natalizumab, Tysabri(®)) were reviewed which comprised all 42 cases of natalizumab-related PML cases since its reintroduction until March 2010.ResultsAll except 2 patients with natalizumab-related PML were managed by discontinuation of natalizumab and plasmapheresis/immunoadsorption (PLEX/IA). Seventeen patients had contrast enhancement of PML lesions on neuroimaging at the time of diagnosis before withdrawal/removal of natalizumab (early-PML-IRIS) and 23 patients developed contrast enhancement only after withdrawal/removal of natalizumab (late-PML-IRIS). All patients developed IRIS. IRIS was defined as worsening of neurologic deficits during the immune reconstitution following discontinuation of natalizumab, corroborated by inflammatory changes on neuroimaging. Following PLEX/IA, JC viral load in CSF increased by >10 fold in those with early-PML-IRIS but <2 fold in late-PML-IRIS. IRIS developed earlier and was more severe in early-PML-IRIS (p < 0.05). At the last follow-up, all patients had worse EDSS scores but this was higher in patients with early-PML-IRIS compared to those with late-PML-IRIS (p > 0.05). Mortality was comparable between the 2 groups, 29.4 ± 11% vs 21.7 ± 8.8%. Corticosteroid therapy during IRIS was associated with better Expanded Disability Status Scale outcome, p < 0.05.ConclusionEarly immunologic rebound in natalizumab-associated PML has worse survival and neurologic outcome. PLEX/IA may accelerate IRIS and its impact on the final outcome is unclear. Corticosteroid therapy provides a modest benefit and needs to be systemically studied in a controlled manner in the management of natalizumab-associated PML-IRIS.
| S-EPMC3174071 | biostudies-literature
Project description: Not available
| S-EPMC9039471 | biostudies-literature
Project description: Not available
| S-EPMC2677527 | biostudies-literature
Project description:BackgroundParadoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) affects ~25% of human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis (CM) after they commence antiretroviral therapy (ART) resulting in significant morbidity and mortality. Genomic studies in cryptococcal meningitis and C-IRIS are rarely performed.MethodsWe assessed whole blood transcriptomic profiles in 54 HIV-infected subjects with CM who developed C-IRIS (27) and compared the results with control subjects (27) who did not experience neurological deterioration over 24 weeks after ART initiation. Samples were analyzed by whole genome microarrays.ResultsThe predictor screening algorithms identified the low expression of the components of interferon-driven antiviral defense pathways, such as interferon-inducible genes, and higher expression of transcripts that encode granulocyte-dependent proinflammatory response molecules as predictive biomarkers of subsequent C-IRIS. Subjects who developed early C-IRIS (occurred within 12 weeks of ART initiation) were characterized by upregulation of biomarker transcripts involved in innate immunity such as the inflammasome pathway, whereas those with late C-IRIS events (after 12 weeks of ART) were characterized by abnormal upregulation of transcripts expressed in T, B, and natural killer cells, such as IFNG, IL27, KLRB1, and others. The AIM2, BEX1, and C1QB were identified as novel biomarkers for both early and late C-IRIS events.ConclusionsAn inability to mount effective interferon-driven antiviral immune response, accompanied by a systemic granulocyte proinflammatory signature, prior to ART initiation, predisposes patients to the development of C-IRIS. Although early and late C-IRIS have seemingly similar clinical manifestations, they have different molecular phenotypes (as categorized by bioinformatics analysis) and are driven by contrasting inflammatory signaling cascades.
| S-EPMC6051466 | biostudies-literature
Project description:Paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome
2019-01-29 | GSE108649 | GEO
Project description:BackgroundImmune reconstitution inflammatory syndrome (IRIS) after initiating highly active antiretroviral therapy (HAART) has not been widely studied in children, especially in resource-poor settings.MethodsRetrospective cohort study of HIV-infected children initiating HAART between 2001 and 2006 at a tertiary pediatric hospital in Lima, Peru. Charts were reviewed for 1 year after HAART initiation. IRIS was defined as a HAART-associated adverse event caused by an infectious or inflammatory condition in patients with documented virologic or immunologic success.ResultsNinety-one children (52% female) received HAART for at least 1 year. Median age at initiation was 5.7 years; 91% were ART naive and 73% had CDC stage C disease. The incidence of IRIS was 19.8 events per 100 person years (95% CI: 11.5-28.0). Median time to IRIS was 6.6 weeks after HAART initiation (range: 2-32 weeks). There were 18 IRIS events, 11 unmasking and 7 paradoxical. These included associations with Mycobacterium tuberculosis in 4 cases, Bacillus Calmette Guerin lymphadenitis in 1 case, varicella zoster virus in 6 cases and herpes simplex labialis in 6 cases. Children who developed IRIS had a higher baseline HIV viral load (P = 0.02) and an indicator of malnutrition (P = 0.007) before HAART initiation.ConclusionIRIS occurred in 20% of HIV-infected children starting HAART in Peru and was associated with more advanced disease and malnutrition. Future research is needed to examine specific risk factors associated with pediatric IRIS to allow prompt identification and treatment of IRIS.
| S-EPMC3514443 | biostudies-literature
Project description:Distinguishing disseminated Mycobacterium marinum from multifocal cutaneous disease in persons with human immunodeficiency virus/AIDS can present a diagnostic challenge, especially in the context of immune reconstitution inflammatory syndrome (IRIS). In this work, we demonstrate the utility of flow cytometry and whole genome sequencing (WGS) to diagnose disseminated M. marinum unmasked by IRIS following initiation of antiretroviral therapy. Flow cytometry demonstrated robust cytokine production by CD4 T cells in response to stimulation with M. marinum lysate. WGS of isolates from distinct lesions was consistent with clonal dissemination, supporting that preexisting disseminated M. marinum disease was uncovered by inflammatory manifestations, consistent with unmasking mycobacterial IRIS.
| S-EPMC8328204 | biostudies-literature
Project description:Access to antiretroviral therapy (ART) is improving worldwide. Immune reconstitution inflammatory syndrome (IRIS) is a common complication of ART initiation. In this review, we provide an overview of clinical and epidemiological features of HIV-associated IRIS, current understanding of pathophysiological mechanisms, available therapy, and preventive strategies. The spectrum of HIV-associated IRIS is described, with a particular focus on three important pathogen-associated forms: tuberculosis-associated IRIS, cryptococcal IRIS, and Kaposi's sarcoma IRIS. While the clinical features and epidemiology are well described, there are major gaps in our understanding of pathophysiology and as a result therapeutic and preventative strategies are suboptimal. Timing of ART initiation is critical to reduce IRIS-associated morbidity. Improved understanding of the pathophysiology of IRIS will hopefully enable improved diagnostic modalities and better targeted treatments to be developed.
| S-EPMC4334287 | biostudies-literature
Project description:BackgroundThe immunopathogenesis of tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) remains incompletely understood, and we know of only 1 disease site-specific study of the underlying immunology; we recently showed that Mycobacterium tuberculosis culture positivity and increased neutrophils in the cerebrospinal fluid (CSF) of patients with tuberculous meningitis (TBM) are associated with TBM-IRIS. In this study we investigated inflammatory mediators at the disease site in patients with TBM-IRIS.MethodsWe performed lumbar puncture at 3-5 time points in human immunodeficiency virus (HIV)-infected patients with TBM (n = 34), including at TBM diagnosis, at initiation of antiretroviral therapy (ART) (day 14), 14 days after ART initiation, at presentation of TBM-IRIS, and 14 days thereafter. We determined the concentrations of 40 mediators in CSF (33 paired with blood) with Luminex or enzyme-linked immunosorbent assays. Findings were compared between patients who developed TBM-IRIS (n = 16) and those who did not (TBM-non-IRIS; n = 18).ResultsAt TBM diagnosis and 2 weeks after ART initiation, TBM-IRIS was associated with severe, compartmentalized inflammation in the CSF, with elevated concentrations of cytokines, chemokines, neutrophil-associated mediators, and matrix metalloproteinases, compared with TBM-non-IRIS. Patients with TBM-non-IRIS whose CSF cultures were positive for M. tuberculosis at TBM diagnosis (n = 6) showed inflammatory responses similar to those seen in patients with TBM-IRIS at both time points. However, at 2 weeks after ART initiation, S100A8/A9 was significantly increased in patients with TBM-IRIS, compared with patients with TBM-non-IRIS whose cultures were positive at baseline.ConclusionsA high baseline M. tuberculosis antigen load drives an inflammatory response that manifests clinically as TBM-IRIS in most, but not all, patients with TBM. Neutrophils and their mediators, especially S100A8/A9, are closely associated with the central nervous system inflammation that characterizes TBM-IRIS.
| S-EPMC4227574 | biostudies-literature
Project description:Cryptococcal meningitis is the most common intracranial infectious fungal disease. After a period of antifungal treatment, as the number of cells in the cerebrospinal fluid decreases, the biochemical indexes improve and the number of cryptococcus reduces, the patient's condition suddenly worsen. Most of the symptoms are severe headache, raised intracranial pressure, together with impaired clinical nerve function. These presentations are often mistaken for a failure of antifungal treatment. In fact it's an encephalitis syndrome which is unrecognized by most clinicians: Immune reconstitution inflammatory syndrome (IRIS). To increase awareness we retrospectively analyzed clinical data of 100 cases of cryptococcal neoformans meningitis, among which 26 patients develop CM-IRIS. All patients have been divided into three groups: Group 1, patients who were not treated with glucocorticoid and didn't experienced IRIS; Group 2, patients who were not treated with glucocorticoid although developed CM-IRIS; Group 3, patients started treatment with glucocorticoid for two weeks with new onset CM-IRIS. Compared with the group treated with glucocorticoid, treatment without glucocorticoid was subjected to a higher risk of incident IRIS. The difference was statistically significant (P < 0.05). Imaging findings demonstrated diseased area of the white matter area, and it looked like commonly in the supratentorial region. Moreover, if it appears in the infratentorial region then must be combined with supratentorial region.
| S-EPMC7305181 | biostudies-literature