ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023
Severe Mycobacterial Immune Reconstitution Inflammatory Syndrome (IRIS) in Advanced Human Immunodeficiency Virus (HIV) Has Features of Hemophagocytic Lymphohistiocytosis and Requires Prolonged Immune Suppression.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06339177 (Hemophagocytic Lymphohistiocytosis), which is not on this map. Cited by 20 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Mycobacterial Immune Reconstitution Inflammatory Syndrome in HIV is Associated With Protein-Altering Variants in Hemophagocytic Lymphohistiocytosis-Related Genes.The Journal of infectious diseases · 2023Trial
- [Characterization of immune reconstitution inflammatory syndrome in a Mexican cohort].Revista medica del Instituto Mexicano del Seguro Social · 2026Observational
- CXCL9 as a novel prognostic marker to identify high-risk adults with hemophagocytic lymphohistiocytosis.Blood · 2026Article
- Clinical analysis of 19 patients with tuberculosis complicated by hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2026Article
- Nutritional and hematological determinants of immune reconstitution and development of a predictive model among virologically suppressed people living with HIV.Frontiers in nutrition · 2026Article
- Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy.Haematologica · 2025Review
- Fatal Cytokine Collision: HLH-AIHA in Advanced AIDS-Case Report and Literature Review.Reports (MDPI) · 2025Article
- Body mass index and hemophagocytic lymphohistiocytosis: a risk assessment in HIV-positive leukemia patients.Annals of medicine and surgery (2012) · 2025Review
- Predicting 30-day mortality in hemophagocytic lymphohistiocytosis: clinical features, biochemical parameters, and machine learning insights.Annals of hematology · 2025Article
- Tuberculosis-triggered cytokine storm with hemophagocytic lymphohistiocytosis and tuberculous spondylitis in an apparently immunocompetent host: a case report and literature review.Frontiers in immunology · 2025Review
- Macrophage Activation Syndrome in Viral Sepsis.Viruses · 2024Review
- Successful rescue TNF-α blocking forHeliyon · 2024Article
- Clonal hematopoiesis in people with advanced HIV and associated inflammatory syndromes.JCI insight · 2024Article
- Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome.Open forum infectious diseases · 2024Article
- Hemophagocytic Lymphohistiocytosis (HLH) in Patients with Tick-Borne Illness: A Scoping Review of 98 Cases.Infectious disease reports · 2024Article
- Article
- Perplexing paradoxical reactions: navigating the complexity of protracted tuberculosis meningitis-a case report.Frontiers in immunology · 2024Article
- Free interleukin-18 is elevated in CD22 CAR T-cell-associated hemophagocytic lymphohistiocytosis-like toxicities.Blood advances · 2023Article
- A Rare Case of Cytomegalovirus Colitis with Subsequent Non-tubercular Mycobacteria Immune Reconstitution Inflammatory Syndrome.Middle East journal of digestive diseases · 2023Article
- Approaching hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPeople with HIV and mycobacterial infections can develop immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy (ART). Severe mycobacterial IRIS has an overlapping clinical phenotype with hemophagocytic lymphohistiocytosis (HLH). We evaluated the pathophysiologic similarities between mycobacterial IRIS and HLH to identify clinical and immune predictors of mycobacterial IRIS severity.
methodsHLH criteria were applied to a longitudinal cohort of 80 patients with HIV (CD4 <100 cells/µL) and mycobacterial infections. Participants were subdivided into IRIS meeting HLH criteria (HLH-IRIS), IRIS without HLH (IRIS), and those without IRIS (non-IRIS). Clinical outcomes were evaluated by regression analyses. Soluble biomarkers and T-cell subsets were assessed at baseline and IRIS-equivalent time points.
resultsHLH-IRIS patients required corticosteroids more frequently (OR: 21.5; 95%CI: 5.6-114.8) and for longer duration (21.2; 95%CI: 10.7-31.7 weeks) than those not meeting HLH criteria. Utilizing decision tree analyses, hemoglobin <9.2 g/dL was the best predictor of HLH-IRIS before ART, whereas ferritin, CXCL9 and sCD25 were most diagnostic for HLH at IRIS onset. At the IRIS timepoint, but not baseline, HLH-IRIS patients had lower regulatory and higher activated T cells along with greater production of IFNγ-IL-18 axis biomarkers compared with both IRIS and non-IRIS groups. Principal component analysis corroborated the distinct clustering of HLH-IRIS patients.
conclusionsSevere mycobacterial IRIS and HLH have an overlapping pathogenesis involving IFNγ and unopposed T-cell activation causing severe inflammatory disease clinically distinguished by hyperferritinemia (hyperferritinemic IRIS [FIRIS]). Hemoglobin, ferritin, CXCL9, and sCD25 identify high-risk patients and may improve risk stratification and therapeutic strategies for mycobacterial IRIS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.