Plasma But Not Cerebrospinal Fluid Interleukin 7 and Interleukin 5 Levels Pre–Antiretroviral Therapy Commencement Predict Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome

Akilimali, Ngomu Akeem; Chang, Christina C.; Muema, Daniel M.; Reddy, Tarylee; Moosa, M Y H; Lewin, Sharon R.; French, Martyn A.; Ndung’u, Thumbi

doi:10.1093/cid/cix598

Cited by 21 publications

(18 citation statements)

References 30 publications

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“…Figure 1 shows the time line of antifungal therapy, ART, C-IRIS events, and sample collection. Comparative demographic details of the original cohort of 130 participants and current substudy are found in Chang et al [ 5 ] and Akilimali et al [ 14 ] respectively, where the C-IRIS group and the control group without neurological deterioration showed no significant difference in age, gender, baseline HIV viral load, or serum cryptococcal antigen titers.…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic Predictors of Paradoxical Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome

Louis

Chang

Shahid

et al. 2018

Open Forum Infectious Diseases

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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.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic Predictors of Paradoxical Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome

Louis

Chang

Shahid

et al. 2018

Open Forum Infectious Diseases

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“…Electronic health records and big data platforms that can integrate genetic, immunologic, clinical, microbial, and environmental variables also hold promise as tools to integrate patient and microbial characteristics and identify measures that correlate with defined clinical and microbial states. Even today, clinical parameters, fungal burden, immunological measures, and cytokine perturbations that correlate with HIV-associated cryptococcosis [29][30][31][32][33] may provide insight into where a patient may lie on the parabola.…”

Section: Finding a Place On The Curvementioning

confidence: 99%

The Damage–Response Framework as a Tool for the Physician-Scientist to Understand the Pathogenesis of Infectious Diseases

Pirofski

Casadevall

2018

The Journal of Infectious Diseases

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“…When it comes to preventing paradoxical C‐IRIS, sufficient and effective antifungal treatment plays an irreplaceable role, because higher residual Cryptococcus burden and related marks such as CRP and IL‐5 indicate higher C‐IRIS incidence . The most simple way to achieve a lower fungal burden before ART is to elongate the antifungal treatment, that is, delaying the initiation of ART.…”

Section: Cryptococcus‐related Immune Reconstitution Inflammatory Syndmentioning

confidence: 99%

Management of human immunodeficiency virus–associated cryptococcal meningitis: Current status and future directions

Shen

2019

Mycoses

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Summary Cryptococcal meningitis (CM) is one of the most common opportunistic infections of acquired immunodeficiency syndrome (AIDS), as well as an important cause of hospitalisation and death. In recent years, the mortality of CM has remained high in HIV/AIDS population, with up to 30%, including within developed countries. The treatment usually encompasses controls of Cryptococcus, HIV, and increased intracranial pressure. Recent progress on the management of HIV‐associated CM mainly centres in optimising induction regimens, looking for appropriate timing of initiating antiretroviral therapy and prevention of symptomatic onset and adverse consequences. This review compared several international guidelines combined with the results from some clinical researches to illustrate the similarities, differences and potential in CM treatment. The present practice is still far from satisfactory, and there remains much to explore due to our limited understanding of the pathogenesis of HIV‐associated CM. Thus, screening and monitoring should be strengthened, and better therapies in line with the actual situation of each country should be discovered.

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Plasma But Not Cerebrospinal Fluid Interleukin 7 and Interleukin 5 Levels Pre–Antiretroviral Therapy Commencement Predict Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome

Cited by 21 publications

References 30 publications

Transcriptomic Predictors of Paradoxical Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome

Transcriptomic Predictors of Paradoxical Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome

The Damage–Response Framework as a Tool for the Physician-Scientist to Understand the Pathogenesis of Infectious Diseases

Management of human immunodeficiency virus–associated cryptococcal meningitis: Current status and future directions

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