scholarly journals Plasma Metabolomics Reveals Dysregulated Metabolic Signatures in HIV-Associated Immune Reconstitution Inflammatory Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Luxin Pei ◽  
Kiyoshi F. Fukutani ◽  
Rafael Tibúrcio ◽  
Adam Rupert ◽  
Eric W. Dahlstrom ◽  
...  
Keyword(s):  
Amino Acid ◽  
Antiretroviral Therapy ◽  
Immune Activation ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Cellular Metabolism ◽  
Targeted Prevention ◽  
Hiv Viral Load ◽  
Inflammatory Syndrome ◽  
The Impact

Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory complication associated with an underlying opportunistic infection that can be observed in HIV-infected individuals shortly after the initiation of antiretroviral therapy, despite successful suppression of HIV viral load and CD4+ T cell recovery. Better understanding of IRIS pathogenesis would allow for targeted prevention and therapeutic approaches. In this study, we sought to evaluate the metabolic perturbations in IRIS across longitudinal time points using an unbiased plasma metabolomics approach as well as integrated analyses to include plasma inflammatory biomarker profile and whole blood transcriptome. We found that many lipid and amino acid metabolites differentiated IRIS from non-IRIS conditions prior to antiretroviral therapy and during the IRIS event, implicating the association between oxidative stress, tryptophan pathway, and lipid mediated signaling and the development of IRIS. Lipid and amino acid metabolic pathways also significantly correlated with inflammatory biomarkers such as IL-12p70 and IL-8 at the IRIS event, indicating the role of cellular metabolism on cell type specific immune activation during the IRIS episode and in turn the impact of immune activation on cellular metabolism. In conclusion, we defined the metabolic profile of IRIS and revealed that perturbations in metabolism may predispose HIV-infected individuals to IRIS development and contribute to the inflammatory manifestations during the IRIS event. Furthermore, our findings expanded our current understanding IRIS pathogenesis and highlighted the significance of lipid and amino acid metabolism in inflammatory complications.

scholarly journals Association Between Plasma Antibody Responses and Risk for Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome

2018 ◽  
Vol 219 (3) ◽  
pp. 420-428 ◽  
Author(s):  
Hyun Ah Yoon ◽  
Antonio Nakouzi ◽  
Christina C Chang ◽  
Mark H Kuniholm ◽  
Leandro J Carreño ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Memory B Cells ◽  
Hiv Viral Load ◽  
Immunodeficiency Virus ◽  
Plasma Antibody ◽  
Inflammatory Syndrome ◽  
The Relationship ◽  
Cd4 T Cell Count

AbstractBackgroundInitiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated.MethodsWe compared plasma levels of immunoglobulins, C. neoformans glucuronoxylomannan (GXM) capsule-specific and laminarin (Lam)-binding IgM and IgG, and percentages of peripheral blood total and memory B cells between 27 HIV-infected patients with CM who developed C-IRIS and 63 who did not, and evaluated associations of these parameters with risk of C-IRIS.ResultsPrior to initiation of ART, plasma IgM, Lam-binding IgM (Lam-IgM), Lam-IgG, and GXM-IgM levels were significantly lower in patients who developed C-IRIS than those who did not. Multivariate analysis revealed significant inverse associations between C-IRIS and IgM (P = .0003), Lam-IgM (P = .0005), Lam-IgG (P = .002), and GXM-IgM (P = .002) independent of age, sex, HIV viral load, CD4+ T-cell count, and cerebrospinal fluid fungal burden. There were no associations between C-IRIS and total or memory B cells.DiscussionAntibody profiles that include plasma IgM, Lam-IgM, Lam-IgG, and/or GXM-IgM may have value in furthering our understanding of C-IRIS pathogenesis and hold promise as candidate biomarkers of C-IRIS risk.

Immune Reconstitution Inflammatory Syndrome

2011 ◽  
Vol 23 (1) ◽  
pp. 90-96 ◽  
Author(s):  
A.R. Tappuni
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
T Regulatory Cells ◽  
Clinical Presentation ◽  
Early Recognition ◽  
Clinical Intervention ◽  
Suppressor Cell ◽  
Life Threatening ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is a phenomenon observed in patients recovering from immunodeficiency. The clinical presentation of IRIS involves the unmasking of covert infections or the worsening of overt conditions. Several causes and pathways have been suggested, most recognizing an inflammatory flare component occurring in the context of rapid immune reconstitution. In HIV-infected patients, IRIS inadvertently occurs as the consequence of successful antiretroviral therapy, and it is affiliated with improvement of the immune function, complicating the course of the disease and presenting treatment challenges to clinicians. The pathogenesis of IRIS is poorly understood, but in recovering HIV patients, its initiation and progression seem to be primarily linked to an increase in CD4+ T-helper and CD8+ T-suppressor cell count and a reduction in T-regulatory cells, all endorsed by exaggerated cytokine release and activity. The clinical presentation of IRIS is usually atypical. The manifestations depend on the trigger antigen, which can be an infective agent (viable or nonviable), a host antigen, or a tumor antigen. Most IRIS cases are self-limiting, but a few cases can be overwhelming and life-threatening; hence, early recognition is important. In most cases, there is no need to discontinue the antiretroviral therapy, although in the more severe cases, other clinical intervention may be necessary.

scholarly journals Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy

2012 ◽  
Vol 54 (4) ◽  
pp. 231-233 ◽  
Author(s):  
Walter de Araujo Eyer-Silva ◽  
Maria Cecília da Fonseca Salgado ◽  
Jorge Francisco da Cunha Pinto ◽  
Fernando Raphael de Almeida Ferry ◽  
Rogério Neves-Motta ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Highly Active Antiretroviral Therapy ◽  
Immune Reconstitution ◽  
Gouty Arthritis ◽  
Infected Male ◽  
Acute Gouty Arthritis ◽  
Highly Active ◽  
History Of ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

scholarly journals Cardiovascular Biomarker Profile on Antiretroviral Therapy Is Not Influenced by History of an IRIS Event in People With HIV and Suppressed Viremia

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Aurelie Gouel-Cheron ◽  
Martha Nason ◽  
Adam Rupert ◽  
Virginia Sheikh ◽  
Greg Robby ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Antiretroviral Therapy ◽  
Chronic Inflammation ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Art Initiation ◽  
History Of ◽  
Cardiovascular Biomarker ◽  
Inflammatory Syndrome

Abstract Immune reconstitution inflammatory syndrome (IRIS) is characterized by release of proinflammatory cytokines and tissue inflammation occurring early after antiretroviral therapy (ART) initiation. The role of previous IRIS events in persistent chronic inflammation in people with HIV is currently unclear. In this retrospective analysis of 143 participants who maintained suppression of HIV viremia, we compared biomarkers related to inflammation, coagulation, and cardiovascular risk after 3 years on ART in participants with and without a history of IRIS. There was no evidence of higher levels of persistent chronic inflammation in people with HIV who had a history of an IRIS event. ClinicalTrials.gov Identifier . NCT00286767.

scholarly journals Declines in Lung Function After Antiretroviral Therapy Initiation in Adults With Human Immunodeficiency Virus and Tuberculosis: A Potential Manifestation of Respiratory Immune Reconstitution Inflammatory Syndrome

2019 ◽  
Vol 70 (8) ◽  
pp. 1750-1753 ◽  
Author(s):  
Sara C Auld ◽  
Pholo Maenetje ◽  
Shruthi Ravimohan ◽  
Drew Weissman ◽  
Itai Ncube ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cohort Study ◽  
Antiretroviral Therapy ◽  
Lung Function ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Research Attention ◽  
Therapy Initiation ◽  
Immunodeficiency Virus ◽  
Inflammatory Syndrome

Abstract End-organ impairment has received relatively little research attention as a possible manifestation of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS). In this prospective cohort study, one-half of adults with human immunodeficiency virus and pulmonary tuberculosis experienced meaningful declines in lung function on antiretroviral therapy, suggesting a role for lung function in TB-IRIS definitions.

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